Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascu... more Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascular calcification is an active and regulated process. Wnt signalling, required for osteoblast function, is also involved in SMC trans-differentiation in both vascular and bone calcification. Sclerostin is an endogenous antagonist of wnt/B catenin signaling pathway. Computed tomography coronary angiography (CTCA) is a non invasive, though expensive and high radiation exposure tool to detect coronary calcification which is expressed as calcium scores (CACS) and is widely used. Hence, there is a need to find innocuous marker such as sclerostin to evaluate CAC score. Following were objectives of the study: 1. To estimate the serum levels of sclerostin, hs-CRP and lipid profile parameters in patients with CAD. 2. To correlate sclerostin level with the coronary artery calcium score (CACS) and other markers of atherosclerosis i.e. hs-CRP, ApoA1, ApoB100, lipid profile and carotid intima media thickness (CIMT) in CAD. A hospital based cross sectional study recruiting 80 subjects was conducted. For comparison subjects were divided in 2 groups CACS=0(n=50) and CACS>0 (n=30) Serum sclerostin levels were estimated by using commercially available ELISA kit. Hs-CRP, ApoA1, ApoB100 and lipid profile parameters by immunoturbidimetry. CACS and CIMT measured by CT angiography and color Doppler. Sclerostin levels were higher in males than females (p value 0 as compared to CACS=0 ( p 0 showed a significantly higher serum sclerostin levels also serum sclerostin levels significantly correlated with hs-CRP, ApoA1, ApoB100 and CIMT. Hence we conclude that serum sclerostin levels can act as a marker of coronary artery calcification in CAD.
Asian Journal of Pharmaceutical and Clinical Research, Mar 7, 2023
Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (... more Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (TSH) measurement along with serum T 3 and T 4 (both free and total). However, TSH is used to distinguish between euthyroid and hyperthyroid patients. Hence, analysis sensitivity of the TSH assay plays a very significant role. Aims and objectives-The aim of the study was to perform the precision study, calculate the randomerror and analytical measurement rangeverification, as well as verify the accuracy of TSH estimation on Finecare™ point of care testing (POCT). Methods: The experimental evaluation was done in preliminary and final parts. The preliminary part calculates random errors, systemic errors, and recovery whereas the final evaluation comprises the implementation of the method comparison between chemiluminescence and immunofluorescence assay (CLIA). Results: In the preliminary evaluation, the inter-assay-high-value sample had CV% was 15 whereas the low-value sample has 13, and the intra-assay had a CV% of 5.8. The recovery test shows 22.22% CV. The final evaluation of the new method Immuno Fluorescence Assay and reference method (CLIA) has a correlation of coefficient 0.9937. Conclusion: POCT reduces pre-analytical error by reducing misidentification of the patient, specimen, and sample handling. This reduces the turnaround time. It helps to improve the quality of care, healthy outcomes, and affordability.
Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a ... more Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a tremendous social and economic impact worldwide, and rapid outspreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being seen in India. Currently, there are two explanations available for the fatal ARDS in COVID-19 cases. Cytokine storm is characterized by unregulated release of various proinflammatory cytokines, i.e., TNF-α, INF-γ, IL2, IL6, IL8, IL12, CCL2, CCL3, and CXCL10, after interaction between SARS-CoV-2 and host immune cells. On the other hand, bradykinin storm is happening due to downregulation of ACE in the lung tissue. Immunomodulatory effects of vitamin D is proved through various studies. There is no individual therapy and vaccination for the SARS-Cov-2; thus, repurposing of available medicines is crucial now. Antiviral, anti-inflammatory, and immuno-boosting effects of vitamin D has proven in many studies. These effects are very relevant for its putative beneficial effect in SARS-CoV-2. Review result: Vitamin D has already been used as a repurposed drug in H5N1 pneumonia. Immunomodulatory and antibacterial role of vitamin D is well established. There are studies suggesting toward the cytokine storm as a main culprit behind deadly ARDS in COVID-19. Vitamin D was found as an anti-inflammatory and lung protective substance. Vitamin D was also found protective against bacterial LPS-induced injury by increasing expression of ACE-II and producing antibacterial protein cathelicidin. Conclusion: Before COVID-19 pandemic, we realized the silent pandemic of vitamin D deficiency. The immunomodulatory, anti-inflammatory, and antibacterial role of vitamin D has been shown in many studies. There are studies which have demonstrated the inverse relationship between vitamin D level and susceptibility to COVID-19. Vitamin-D also plays a crucial role in limiting the fibrosis in the damaged pulmonary tissue and also responsible for deciding overall morbidity of the patient. Thus, it is imperative to think about the potential of vitamin D as a repurposed drug for COVID-19 cases.
Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approxima... more Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approximately 42 million people worldwide. Juvenile myoclonic epilepsy (JME) is a common form of idiopathic generalized epilepsy representing 5-10% of all epilepsy cases. Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood onset, the cause of which may be symptomatic, i.e., secondary to an underlying brain disorder or cryptogenic, i.e., with no known cause. Sodium channels are integral membrane proteins which play a central role in neuronal membrane excitability and action potential generation. Alpha subunit of voltage gated sodium channels encoded by SCN1A, SCN2A and other genes is pivotal for neuronal signalling. It was planned to analyse the roles of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms in the pathophysiology and risk JME and LGS in the Indian population. Methods: A total of 50 JME patients, 50 LGS Patients and 100 age and sex matched healthy volunteers were recruited in this study. The genotyping of SCN1A Thr1067Ala i.e., 3184 A>G (rs2298771) and SCN2A Arg19Lys i.e., 56 G>A (rs17183814) polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The SCN1A Thr1067Ala polymorphism genotypic distribution in LGS was significantly different from the normal population (P=0.008), with mutant homozygous (GG) plus heterozygous (AG) genotypes' percentage in LGS patients (16%) being lower than in healthy controls (24%). Frequency of the mutant 'G' allele of this SNP in LGS patients was 0.1, while it was 0.2 in control subjects (P=0.04). These observations which suggest a protective role of SCN1A Thr1067Ala polymorphism in LGS, were in sync with computation of an odds ratio of 0.21 (95% CI 0.07 to 0.66, p=0.005) for the GG genotype in LGS patients. Though no correlation of SCN1A Thr1067Ala SNP with the severity of disease phenotype in LGS viz. frequency/duration of seizures etc. was noted, a conflicting finding was the significant association of its mutant genotypes with an early age of onset of the syndrome (p=0.007). Contrary to the findings in SCN1A Thr1067Ala, in case of SCN2A Arg19Lys polymorphism, though a significantly different genotypic distribution was present in LGS, in comparison to normal population (p=0.03), the mutant homozygous (AA) and heterozygous (GA) combined percentage in LGS patients (16%) was greater than in healthy controls (11%). This was complemented by observation of an odds ratio of 4.24 (95% CI 1.15 to 15.55, p=0.029, in case of LGS patients with heterozygous (GA) genotype, indicative of an increased disease susceptibility. Unlike LGS, in JME patients no significant differences in genotypic/allelic frequencies of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms were noted and the associated odds ratios for mutant genotypes were also non-significant. Conclusion: The SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms may play contrary roles in the pathophysiology of LGS. Inheritance of SCN1A Thr1067Ala mutant allele decreases the susceptibility for LGS occurrence, and may hamper Na + channels opening and neuronal excitability. On the other hand, the mutant allele of SCN2A Arg19Lys polymorphism confers an increased risk for development of LGS, consequent to a likely facilitatory effect on action potential generation and misfiring in neurons. Neither of these two SNPs appears to influence the pathogenesis/susceptibility to JME.
Asian Journal of Pharmaceutical and Clinical Research
Objectives: The undergraduate biochemistry practical’s are the routine test performed in all the ... more Objectives: The undergraduate biochemistry practical’s are the routine test performed in all the medical laboratories. Few of these have been certified practical by competency-based medical education. This will help the teachers access the depth of theoretical and practical knowledge as well as judge their communication skills. To detect the basic concept of quality control in the biochemistry laboratory. Methods: Quantitative analysis was conducted with a purposive sample, at the Noida International institute of medical sciences by the department of biochemistry. 150 students performed the practical on serum albumin in two batches after the demonstration by the faculty. The results were collected through Google forms. The mean, SD, coefficient of variation, and bias were calculated. Results: Both batches showed significant improvement in repeating the practical. Batch a performance was markedly improved after disclosing the optical density of the standard. Conclusion: Teaching basi...
Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progress... more Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progression CML has three phases: chronic phase, accelerated phase and blast crisis phase. Most of the patients remain undiagnosed until and unless specific test for Philadelphia chromosome was performed. So if CML Patients remains untreated; progress from chronic phase to accelerated and then blast crisis which is medical emergency. So identification of progression of CML from CP to AP and AP to BC in early phase before terminal blast crisis phase is very important. The mechanism that leads to disease progression is not exactly known. There are many possible Genetic and Epigenetic Mechanism that leads to CML progression. Promoter hypermethylation is one of the possible epigenetic mechanisms that leads to inactivation of tumor suppressor gene in hematological malignancies. GADD45G is one of the tumor suppressor gene among panel of tumor suppressor genes involved in cancers especially hematologic...
Asian Journal of Pharmaceutical and Clinical Research
Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (... more Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (TSH) measurement along with serum T3 and T4 (both free and total). However, TSH is used to distinguish between euthyroid and hyperthyroid patients. Hence, analysis sensitivity of the TSH assay plays a very significant role. Aims and objectives – The aim of the study was to perform the precision study, calculate the randomerror and analytical measurement rangeverification, as well as verify the accuracy of TSH estimation on Finecare™ point of care testing (POCT). Methods: The experimental evaluation was done in preliminary and final parts. The preliminary part calculates random errors, systemic errors, and recovery whereas the final evaluation comprises the implementation of the method comparison between chemiluminescence and immunofluorescence assay (CLIA). Results: In the preliminary evaluation, the inter-assay-high-value sample had CV% was 15 whereas the low-value sample has 13, and th...
Background: Chronic Myeloid Leukemia( CML) is the first disease to be linked to a specific gene a... more Background: Chronic Myeloid Leukemia( CML) is the first disease to be linked to a specific gene alteration i.e. the BCR-ABL1 fusion gene.The BCR-ABL1 protein posseses a constitutively active tyrosine kinase activity,and Imatinib a tyrosine kinase inhibitor (TKI), is the first line treatment for CML. However Imatinib has been found unable to completely eliminate leukemic stem cells,which escape Imatinib induced apoptosis. Increased expression of MAPK pathway proteins in response to Imatinib therapy has been suggested as a probable cause of leukemic stem cells persistence. Oncomir-1 is a polycistronic micro RNA complex, which encodes six micro RNAs- miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1. Increased oncomir-1 expression which regulates MAPK pathway at various levels, and directly regulates pre-apoptotic proteins containing BH domain, has been suggested as a reason for disease persistence and relapse of CML. This study evaluated the pathogenetic role of miR-17 compon...
Aim: To review pathogenesis of cytokine storm in COVID-19 cases. Background: Human coronaviruses ... more Aim: To review pathogenesis of cytokine storm in COVID-19 cases. Background: Human coronaviruses (hCoV) mainly infect upper airways and cause seasonal mild to moderate cold-like respiratory symptoms or severe pneumonia leading to fatal acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent clinical investigation reveals that mild COVID-19 patients had high level of IL1B, IFN-γ, CXCL10/IP-10, and CCL2/MCP-1, while patients requiring ICU admission had higher level of GCSF, CXCL10/IP-10, CCL2/MCP-1, and CCL3/MIP-1A, indicating inflammatory cytokine release is critical in COVID-19 progression. IL-1 and IL-6 are responsible for elevation of acute-phase reactants, such as C-reactive protein, serum amyloid A, fibrinogen, hepcidin, and inhibition of albumin synthesis which all together causes a procoagulant environment. In a meta-analysis including nine studies (total 1426 patients), mean IL-6 levels were more than 3 times higher in patients with complicated COVID-19 compared to those with uncomplicated disease, and high IL-6 levels were associated with mortality risk. IL-6 is an important marker of inflammation and can guide the clinicians in recognizing patients with severe COVID-19 early in the disease course. Delay in the interferon release and presence of LPS by secondary bacterial infections increases the severity of cytokine storm. Thus, commencement of early broad-spectrum antibiotic course is advisable. Cytokine storm appears after first week of symptoms when viral load starts decreasing, and this indicates the immunopathogenesis of the ARDS. Conclusion: The aberrant release of multiple cytokines in COVID-19 produces immunopathogenic damage to tissues and organs, even while the immune response tries to overcome the evading mechanisms of virus. Delay in the interferon release and presence of lipopolysaccharide by secondary bacterial infections increase the severity of cytokine storm. IL-6 could be used as a potential marker for severity of the ARDS. However, anti-IL6 antibody Tocilizumab failed to prove effective in clinical trials. Corticosteroid therapy is being given for moderate and severe cases of ARDS, but it needs a very fine balance to outweigh immunosuppressive effects.
Objective – To measure the expression of micro RNA 19b in peripheral blood leukocytes of newly di... more Objective – To measure the expression of micro RNA 19b in peripheral blood leukocytes of newly diagnosed patients of Chronic Myeloid Leukemia and study the effect of standard care with Imatinib Mesylate on the expression level of above miR. Study design – Hospital based Case-Control study. Setting – Department Of Biochemistry, Maulana Azad Medical College, New Delhi, Department Of Pathology, MAMC, New Delhi, Department of Medicine, LNJP Hospital, New Delhi. Subjects – 35 newly diagnosed CML cases in chronic phase of disease and 35 age and sex matched healthy controls. Methods – The expression of microRNA 19b in peripheral blood mononuclear cells (PBMCs) of 35 CML cases in chronic phase, in comparison to 35 age and sex matched healthy control subjects was carried out. RNA was extracted from PBMCs of both CML patients and controls using Trizol reagent. Expression studies were performed by SYBR green based qRT-PCR and results were expressed as mean fold change. Expression of miR-19b...
Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascu... more Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascular calcification is an active and regulated process. Wnt signalling, required for osteoblast function, is also involved in SMC trans-differentiation in both vascular and bone calcification. Sclerostin is an endogenous antagonist of wnt/B catenin signaling pathway. Computed tomography coronary angiography (CTCA) is a non invasive, though expensive and high radiation exposure tool to detect coronary calcification which is expressed as calcium scores (CACS) and is widely used. Hence, there is a need to find innocuous marker such as sclerostin to evaluate CAC score. Following were objectives of the study: 1. To estimate the serum levels of sclerostin, hs-CRP and lipid profile parameters in patients with CAD. 2. To correlate sclerostin level with the coronary artery calcium score (CACS) and other markers of atherosclerosis i.e. hs-CRP, ApoA1, ApoB100, lipid profile and carotid intima media...
Uric acid is considered to be an important risk factor for the development of type 2 diabetes mel... more Uric acid is considered to be an important risk factor for the development of type 2 diabetes mellitus (T2D) and a determinant of incidence of T2D in adults with glucose intolerance. There is conflicting finding regarding the trend of serum uric acid level in different glycemic status. Therefore this study has been aimed to investigate the association of serum uric acid level with glycemic parameters in prediabetic and diabetic individuals attending the tertiary care hospital in Uttarakhand, An observational study was conducted in 721 individuals based on data collected from Biochemistry log book of AIIMS Rishikesh maintained from October 2014 to September 2016. The enzymatic method was carried out for measurement of Serum uric acid [ (Uricase) and blood glucose (BG) (Hexokinase)] level, and HbA1c was determined by immune inhibition method. Out of 721 individuals (410 male and 311female) 118 and 504 individuals belonged to prediabetes and T2D respectively. Prediabetic individual...
Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progress... more Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progression CML has three phases: chronic phase, accelerated phase and blast crisis phase. Most of the patients remain undiagnosed until and unless specific test for Philadelphia chromosome was performed. So if CML Patients remains untreated; progress from chronic phase to accelerated and then blast crisis which is medical emergency. So identification of progression of CML from CP to AP and AP to BC in early phase before terminal blast crisis phase is very important. The mechanism that leads to disease progression is not exactly known. There are many possible Genetic and Epigenetic Mechanism that leads to CML progression. Promoter hypermethylation is one of the possible epigenetic mechanisms that leads to inactivation of tumor suppressor gene in hematological malignancies. GADD45G is one of the tumor suppressor gene among panel of tumor suppressor genes involved in cancers especially hematologic...
Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a ... more Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a tremendous social and economic impact worldwide, and rapid outspreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being seen in India. Currently, there are two explanations available for the fatal ARDS in COVID-19 cases. Cytokine storm is characterized by unregulated release of various proinflammatory cytokines, i.e., TNF-α, INF-γ, IL2, IL6, IL8, IL12, CCL2, CCL3, and CXCL10, after interaction between SARS-CoV-2 and host immune cells. On the other hand, bradykinin storm is happening due to downregulation of ACE in the lung tissue. Immunomodulatory effects of vitamin D is proved through various studies. There is no individual therapy and vaccination for the SARS-Cov-2; thus, repurposing of available medicines is crucial now. Antiviral, anti-inflammatory, and immuno-boosting effects of vitamin D has proven in many studies. These effects are very relevant for its putative beneficial effect in SARS-CoV-2. Review result: Vitamin D has already been used as a repurposed drug in H5N1 pneumonia. Immunomodulatory and antibacterial role of vitamin D is well established. There are studies suggesting toward the cytokine storm as a main culprit behind deadly ARDS in COVID-19. Vitamin D was found as an anti-inflammatory and lung protective substance. Vitamin D was also found protective against bacterial LPS-induced injury by increasing expression of ACE-II and producing antibacterial protein cathelicidin. Conclusion: Before COVID-19 pandemic, we realized the silent pandemic of vitamin D deficiency. The immunomodulatory, anti-inflammatory, and antibacterial role of vitamin D has been shown in many studies. There are studies which have demonstrated the inverse relationship between vitamin D level and susceptibility to COVID-19. Vitamin-D also plays a crucial role in limiting the fibrosis in the damaged pulmonary tissue and also responsible for deciding overall morbidity of the patient. Thus, it is imperative to think about the potential of vitamin D as a repurposed drug for COVID-19 cases.
MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a... more MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a therapeutic target in various cancers. In this study, we analyzed alterations in the expression of miR-486-5p in chronic Myeloid Leukemia (CML) patients. Initially, the expression of miR-486-5p was studied in the BCR-ABL1+ve CML K562 cell line by quantitative realtime polymerase chain reaction (qRT-PCR). The results indicated that the miR-486-5p expression was significantly upregulated in K562 cells after imatinib exposure, as compared to untreated K562 cells (p-value = 0.047). These observations were corroborated by a hospital-based study of the miR-486-5p expression in peripheral blood leucocytes of 36 CML patients in the chronic phase (CP) and compared with age and sex-matched healthy volunteers as control subjects. qRT-PCR-based quantification revealed significant downregulation of the miR-486-5p expression in newly diagnosed untreated CP-CML patients' samples (2 −ΔCt = 13.19 ± 14.41) as compared to control samples (2 −ΔCt = 254.5 ± 274.8) (p-value < 0.0001). Levels of miR-486-5p were found to be distinctly elevated in the post-imatinib treatment samples of CML patients (2 −ΔCt = 469.7 ± 312.9) as compared to pre-treatment samples (p-value < 0.0001). CML patients' clinical and hematological responses to imatinib therapy (oral dose of 400 mg OD) were monitored for 12 months. The correlation of pre-treatment miR-486-5p levels with Sokal score indicated that patients with a higher expression of miR-486-5p had better prognoses. Patients with higher pre-imatinib miR-486-5p levels also showed a major hematologic response to imatinib in a shorter time and vice versa. To the best of our knowledge, this is the first report of alterations in the miR-486-5p expression in peripheral blood leucocytes of CML patients. Our observations support a tumor suppressor role of miR-486-5p in CML. The downregulation of the miR-486-5p expression may be critically important in the disease progression of CML patients. The upregulation of the miR-486-5p expression in post-imatinib exposure K562 cells and CML patients after 12 months of imatinib treatment suggests an onco-suppressor effector role of miR-486-5p in the BCR-ABL downstream signaling pathway. miR-486-5p can be explored as a novel biomarker for the early detection of CML.
Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approxima... more Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approximately 42 million people worldwide. Juvenile myoclonic epilepsy (JME) is a common form of idiopathic generalized epilepsy representing 5-10% of all epilepsy cases. Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood onset, the cause of which may be symptomatic, i.e., secondary to an underlying brain disorder or cryptogenic, i.e., with no known cause. Sodium channels are integral membrane proteins which play a central role in neuronal membrane excitability and action potential generation. Alpha subunit of voltage gated sodium channels encoded by SCN1A, SCN2A and other genes is pivotal for neuronal signalling. It was planned to analyse the roles of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms in the pathophysiology and risk JME and LGS in the Indian population. Methods: A total of 50 JME patients, 50 LGS Patients and 100 age and sex matched healthy volunteers were recruited in this study. The genotyping of SCN1A Thr1067Ala i.e., 3184 A>G (rs2298771) and SCN2A Arg19Lys i.e., 56 G>A (rs17183814) polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The SCN1A Thr1067Ala polymorphism genotypic distribution in LGS was significantly different from the normal population (P=0.008), with mutant homozygous (GG) plus heterozygous (AG) genotypes' percentage in LGS patients (16%) being lower than in healthy controls (24%). Frequency of the mutant 'G' allele of this SNP in LGS patients was 0.1, while it was 0.2 in control subjects (P=0.04). These observations which suggest a protective role of SCN1A Thr1067Ala polymorphism in LGS, were in sync with computation of an odds ratio of 0.21 (95% CI 0.07 to 0.66, p=0.005) for the GG genotype in LGS patients. Though no correlation of SCN1A Thr1067Ala SNP with the severity of disease phenotype in LGS viz. frequency/duration of seizures etc. was noted, a conflicting finding was the significant association of its mutant genotypes with an early age of onset of the syndrome (p=0.007). Contrary to the findings in SCN1A Thr1067Ala, in case of SCN2A Arg19Lys polymorphism, though a significantly different genotypic distribution was present in LGS, in comparison to normal population (p=0.03), the mutant homozygous (AA) and heterozygous (GA) combined percentage in LGS patients (16%) was greater than in healthy controls (11%). This was complemented by observation of an odds ratio of 4.24 (95% CI 1.15 to 15.55, p=0.029, in case of LGS patients with heterozygous (GA) genotype, indicative of an increased disease susceptibility. Unlike LGS, in JME patients no significant differences in genotypic/allelic frequencies of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms were noted and the associated odds ratios for mutant genotypes were also non-significant. Conclusion: The SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms may play contrary roles in the pathophysiology of LGS. Inheritance of SCN1A Thr1067Ala mutant allele decreases the susceptibility for LGS occurrence, and may hamper Na + channels opening and neuronal excitability. On the other hand, the mutant allele of SCN2A Arg19Lys polymorphism confers an increased risk for development of LGS, consequent to a likely facilitatory effect on action potential generation and misfiring in neurons. Neither of these two SNPs appears to influence the pathogenesis/susceptibility to JME.
Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascu... more Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascular calcification is an active and regulated process. Wnt signalling, required for osteoblast function, is also involved in SMC trans-differentiation in both vascular and bone calcification. Sclerostin is an endogenous antagonist of wnt/B catenin signaling pathway. Computed tomography coronary angiography (CTCA) is a non invasive, though expensive and high radiation exposure tool to detect coronary calcification which is expressed as calcium scores (CACS) and is widely used. Hence, there is a need to find innocuous marker such as sclerostin to evaluate CAC score. Following were objectives of the study: 1. To estimate the serum levels of sclerostin, hs-CRP and lipid profile parameters in patients with CAD. 2. To correlate sclerostin level with the coronary artery calcium score (CACS) and other markers of atherosclerosis i.e. hs-CRP, ApoA1, ApoB100, lipid profile and carotid intima media thickness (CIMT) in CAD. A hospital based cross sectional study recruiting 80 subjects was conducted. For comparison subjects were divided in 2 groups CACS=0(n=50) and CACS>0 (n=30) Serum sclerostin levels were estimated by using commercially available ELISA kit. Hs-CRP, ApoA1, ApoB100 and lipid profile parameters by immunoturbidimetry. CACS and CIMT measured by CT angiography and color Doppler. Sclerostin levels were higher in males than females (p value 0 as compared to CACS=0 ( p 0 showed a significantly higher serum sclerostin levels also serum sclerostin levels significantly correlated with hs-CRP, ApoA1, ApoB100 and CIMT. Hence we conclude that serum sclerostin levels can act as a marker of coronary artery calcification in CAD.
Asian Journal of Pharmaceutical and Clinical Research, Mar 7, 2023
Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (... more Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (TSH) measurement along with serum T 3 and T 4 (both free and total). However, TSH is used to distinguish between euthyroid and hyperthyroid patients. Hence, analysis sensitivity of the TSH assay plays a very significant role. Aims and objectives-The aim of the study was to perform the precision study, calculate the randomerror and analytical measurement rangeverification, as well as verify the accuracy of TSH estimation on Finecare™ point of care testing (POCT). Methods: The experimental evaluation was done in preliminary and final parts. The preliminary part calculates random errors, systemic errors, and recovery whereas the final evaluation comprises the implementation of the method comparison between chemiluminescence and immunofluorescence assay (CLIA). Results: In the preliminary evaluation, the inter-assay-high-value sample had CV% was 15 whereas the low-value sample has 13, and the intra-assay had a CV% of 5.8. The recovery test shows 22.22% CV. The final evaluation of the new method Immuno Fluorescence Assay and reference method (CLIA) has a correlation of coefficient 0.9937. Conclusion: POCT reduces pre-analytical error by reducing misidentification of the patient, specimen, and sample handling. This reduces the turnaround time. It helps to improve the quality of care, healthy outcomes, and affordability.
Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a ... more Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a tremendous social and economic impact worldwide, and rapid outspreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being seen in India. Currently, there are two explanations available for the fatal ARDS in COVID-19 cases. Cytokine storm is characterized by unregulated release of various proinflammatory cytokines, i.e., TNF-α, INF-γ, IL2, IL6, IL8, IL12, CCL2, CCL3, and CXCL10, after interaction between SARS-CoV-2 and host immune cells. On the other hand, bradykinin storm is happening due to downregulation of ACE in the lung tissue. Immunomodulatory effects of vitamin D is proved through various studies. There is no individual therapy and vaccination for the SARS-Cov-2; thus, repurposing of available medicines is crucial now. Antiviral, anti-inflammatory, and immuno-boosting effects of vitamin D has proven in many studies. These effects are very relevant for its putative beneficial effect in SARS-CoV-2. Review result: Vitamin D has already been used as a repurposed drug in H5N1 pneumonia. Immunomodulatory and antibacterial role of vitamin D is well established. There are studies suggesting toward the cytokine storm as a main culprit behind deadly ARDS in COVID-19. Vitamin D was found as an anti-inflammatory and lung protective substance. Vitamin D was also found protective against bacterial LPS-induced injury by increasing expression of ACE-II and producing antibacterial protein cathelicidin. Conclusion: Before COVID-19 pandemic, we realized the silent pandemic of vitamin D deficiency. The immunomodulatory, anti-inflammatory, and antibacterial role of vitamin D has been shown in many studies. There are studies which have demonstrated the inverse relationship between vitamin D level and susceptibility to COVID-19. Vitamin-D also plays a crucial role in limiting the fibrosis in the damaged pulmonary tissue and also responsible for deciding overall morbidity of the patient. Thus, it is imperative to think about the potential of vitamin D as a repurposed drug for COVID-19 cases.
Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approxima... more Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approximately 42 million people worldwide. Juvenile myoclonic epilepsy (JME) is a common form of idiopathic generalized epilepsy representing 5-10% of all epilepsy cases. Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood onset, the cause of which may be symptomatic, i.e., secondary to an underlying brain disorder or cryptogenic, i.e., with no known cause. Sodium channels are integral membrane proteins which play a central role in neuronal membrane excitability and action potential generation. Alpha subunit of voltage gated sodium channels encoded by SCN1A, SCN2A and other genes is pivotal for neuronal signalling. It was planned to analyse the roles of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms in the pathophysiology and risk JME and LGS in the Indian population. Methods: A total of 50 JME patients, 50 LGS Patients and 100 age and sex matched healthy volunteers were recruited in this study. The genotyping of SCN1A Thr1067Ala i.e., 3184 A>G (rs2298771) and SCN2A Arg19Lys i.e., 56 G>A (rs17183814) polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The SCN1A Thr1067Ala polymorphism genotypic distribution in LGS was significantly different from the normal population (P=0.008), with mutant homozygous (GG) plus heterozygous (AG) genotypes' percentage in LGS patients (16%) being lower than in healthy controls (24%). Frequency of the mutant 'G' allele of this SNP in LGS patients was 0.1, while it was 0.2 in control subjects (P=0.04). These observations which suggest a protective role of SCN1A Thr1067Ala polymorphism in LGS, were in sync with computation of an odds ratio of 0.21 (95% CI 0.07 to 0.66, p=0.005) for the GG genotype in LGS patients. Though no correlation of SCN1A Thr1067Ala SNP with the severity of disease phenotype in LGS viz. frequency/duration of seizures etc. was noted, a conflicting finding was the significant association of its mutant genotypes with an early age of onset of the syndrome (p=0.007). Contrary to the findings in SCN1A Thr1067Ala, in case of SCN2A Arg19Lys polymorphism, though a significantly different genotypic distribution was present in LGS, in comparison to normal population (p=0.03), the mutant homozygous (AA) and heterozygous (GA) combined percentage in LGS patients (16%) was greater than in healthy controls (11%). This was complemented by observation of an odds ratio of 4.24 (95% CI 1.15 to 15.55, p=0.029, in case of LGS patients with heterozygous (GA) genotype, indicative of an increased disease susceptibility. Unlike LGS, in JME patients no significant differences in genotypic/allelic frequencies of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms were noted and the associated odds ratios for mutant genotypes were also non-significant. Conclusion: The SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms may play contrary roles in the pathophysiology of LGS. Inheritance of SCN1A Thr1067Ala mutant allele decreases the susceptibility for LGS occurrence, and may hamper Na + channels opening and neuronal excitability. On the other hand, the mutant allele of SCN2A Arg19Lys polymorphism confers an increased risk for development of LGS, consequent to a likely facilitatory effect on action potential generation and misfiring in neurons. Neither of these two SNPs appears to influence the pathogenesis/susceptibility to JME.
Asian Journal of Pharmaceutical and Clinical Research
Objectives: The undergraduate biochemistry practical’s are the routine test performed in all the ... more Objectives: The undergraduate biochemistry practical’s are the routine test performed in all the medical laboratories. Few of these have been certified practical by competency-based medical education. This will help the teachers access the depth of theoretical and practical knowledge as well as judge their communication skills. To detect the basic concept of quality control in the biochemistry laboratory. Methods: Quantitative analysis was conducted with a purposive sample, at the Noida International institute of medical sciences by the department of biochemistry. 150 students performed the practical on serum albumin in two batches after the demonstration by the faculty. The results were collected through Google forms. The mean, SD, coefficient of variation, and bias were calculated. Results: Both batches showed significant improvement in repeating the practical. Batch a performance was markedly improved after disclosing the optical density of the standard. Conclusion: Teaching basi...
Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progress... more Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progression CML has three phases: chronic phase, accelerated phase and blast crisis phase. Most of the patients remain undiagnosed until and unless specific test for Philadelphia chromosome was performed. So if CML Patients remains untreated; progress from chronic phase to accelerated and then blast crisis which is medical emergency. So identification of progression of CML from CP to AP and AP to BC in early phase before terminal blast crisis phase is very important. The mechanism that leads to disease progression is not exactly known. There are many possible Genetic and Epigenetic Mechanism that leads to CML progression. Promoter hypermethylation is one of the possible epigenetic mechanisms that leads to inactivation of tumor suppressor gene in hematological malignancies. GADD45G is one of the tumor suppressor gene among panel of tumor suppressor genes involved in cancers especially hematologic...
Asian Journal of Pharmaceutical and Clinical Research
Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (... more Objective: Thyroid diseases can be diagnosed and monitored by serum thyroid stimulating hormone (TSH) measurement along with serum T3 and T4 (both free and total). However, TSH is used to distinguish between euthyroid and hyperthyroid patients. Hence, analysis sensitivity of the TSH assay plays a very significant role. Aims and objectives – The aim of the study was to perform the precision study, calculate the randomerror and analytical measurement rangeverification, as well as verify the accuracy of TSH estimation on Finecare™ point of care testing (POCT). Methods: The experimental evaluation was done in preliminary and final parts. The preliminary part calculates random errors, systemic errors, and recovery whereas the final evaluation comprises the implementation of the method comparison between chemiluminescence and immunofluorescence assay (CLIA). Results: In the preliminary evaluation, the inter-assay-high-value sample had CV% was 15 whereas the low-value sample has 13, and th...
Background: Chronic Myeloid Leukemia( CML) is the first disease to be linked to a specific gene a... more Background: Chronic Myeloid Leukemia( CML) is the first disease to be linked to a specific gene alteration i.e. the BCR-ABL1 fusion gene.The BCR-ABL1 protein posseses a constitutively active tyrosine kinase activity,and Imatinib a tyrosine kinase inhibitor (TKI), is the first line treatment for CML. However Imatinib has been found unable to completely eliminate leukemic stem cells,which escape Imatinib induced apoptosis. Increased expression of MAPK pathway proteins in response to Imatinib therapy has been suggested as a probable cause of leukemic stem cells persistence. Oncomir-1 is a polycistronic micro RNA complex, which encodes six micro RNAs- miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1. Increased oncomir-1 expression which regulates MAPK pathway at various levels, and directly regulates pre-apoptotic proteins containing BH domain, has been suggested as a reason for disease persistence and relapse of CML. This study evaluated the pathogenetic role of miR-17 compon...
Aim: To review pathogenesis of cytokine storm in COVID-19 cases. Background: Human coronaviruses ... more Aim: To review pathogenesis of cytokine storm in COVID-19 cases. Background: Human coronaviruses (hCoV) mainly infect upper airways and cause seasonal mild to moderate cold-like respiratory symptoms or severe pneumonia leading to fatal acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent clinical investigation reveals that mild COVID-19 patients had high level of IL1B, IFN-γ, CXCL10/IP-10, and CCL2/MCP-1, while patients requiring ICU admission had higher level of GCSF, CXCL10/IP-10, CCL2/MCP-1, and CCL3/MIP-1A, indicating inflammatory cytokine release is critical in COVID-19 progression. IL-1 and IL-6 are responsible for elevation of acute-phase reactants, such as C-reactive protein, serum amyloid A, fibrinogen, hepcidin, and inhibition of albumin synthesis which all together causes a procoagulant environment. In a meta-analysis including nine studies (total 1426 patients), mean IL-6 levels were more than 3 times higher in patients with complicated COVID-19 compared to those with uncomplicated disease, and high IL-6 levels were associated with mortality risk. IL-6 is an important marker of inflammation and can guide the clinicians in recognizing patients with severe COVID-19 early in the disease course. Delay in the interferon release and presence of LPS by secondary bacterial infections increases the severity of cytokine storm. Thus, commencement of early broad-spectrum antibiotic course is advisable. Cytokine storm appears after first week of symptoms when viral load starts decreasing, and this indicates the immunopathogenesis of the ARDS. Conclusion: The aberrant release of multiple cytokines in COVID-19 produces immunopathogenic damage to tissues and organs, even while the immune response tries to overcome the evading mechanisms of virus. Delay in the interferon release and presence of lipopolysaccharide by secondary bacterial infections increase the severity of cytokine storm. IL-6 could be used as a potential marker for severity of the ARDS. However, anti-IL6 antibody Tocilizumab failed to prove effective in clinical trials. Corticosteroid therapy is being given for moderate and severe cases of ARDS, but it needs a very fine balance to outweigh immunosuppressive effects.
Objective – To measure the expression of micro RNA 19b in peripheral blood leukocytes of newly di... more Objective – To measure the expression of micro RNA 19b in peripheral blood leukocytes of newly diagnosed patients of Chronic Myeloid Leukemia and study the effect of standard care with Imatinib Mesylate on the expression level of above miR. Study design – Hospital based Case-Control study. Setting – Department Of Biochemistry, Maulana Azad Medical College, New Delhi, Department Of Pathology, MAMC, New Delhi, Department of Medicine, LNJP Hospital, New Delhi. Subjects – 35 newly diagnosed CML cases in chronic phase of disease and 35 age and sex matched healthy controls. Methods – The expression of microRNA 19b in peripheral blood mononuclear cells (PBMCs) of 35 CML cases in chronic phase, in comparison to 35 age and sex matched healthy control subjects was carried out. RNA was extracted from PBMCs of both CML patients and controls using Trizol reagent. Expression studies were performed by SYBR green based qRT-PCR and results were expressed as mean fold change. Expression of miR-19b...
Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascu... more Coronary artery calcification is an emerging marker being used to evaluate the risk of CAD. Vascular calcification is an active and regulated process. Wnt signalling, required for osteoblast function, is also involved in SMC trans-differentiation in both vascular and bone calcification. Sclerostin is an endogenous antagonist of wnt/B catenin signaling pathway. Computed tomography coronary angiography (CTCA) is a non invasive, though expensive and high radiation exposure tool to detect coronary calcification which is expressed as calcium scores (CACS) and is widely used. Hence, there is a need to find innocuous marker such as sclerostin to evaluate CAC score. Following were objectives of the study: 1. To estimate the serum levels of sclerostin, hs-CRP and lipid profile parameters in patients with CAD. 2. To correlate sclerostin level with the coronary artery calcium score (CACS) and other markers of atherosclerosis i.e. hs-CRP, ApoA1, ApoB100, lipid profile and carotid intima media...
Uric acid is considered to be an important risk factor for the development of type 2 diabetes mel... more Uric acid is considered to be an important risk factor for the development of type 2 diabetes mellitus (T2D) and a determinant of incidence of T2D in adults with glucose intolerance. There is conflicting finding regarding the trend of serum uric acid level in different glycemic status. Therefore this study has been aimed to investigate the association of serum uric acid level with glycemic parameters in prediabetic and diabetic individuals attending the tertiary care hospital in Uttarakhand, An observational study was conducted in 721 individuals based on data collected from Biochemistry log book of AIIMS Rishikesh maintained from October 2014 to September 2016. The enzymatic method was carried out for measurement of Serum uric acid [ (Uricase) and blood glucose (BG) (Hexokinase)] level, and HbA1c was determined by immune inhibition method. Out of 721 individuals (410 male and 311female) 118 and 504 individuals belonged to prediabetes and T2D respectively. Prediabetic individual...
Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progress... more Background: Chronic Myelogenous Leukemia (CML) is hematological cancer. Based on disease progression CML has three phases: chronic phase, accelerated phase and blast crisis phase. Most of the patients remain undiagnosed until and unless specific test for Philadelphia chromosome was performed. So if CML Patients remains untreated; progress from chronic phase to accelerated and then blast crisis which is medical emergency. So identification of progression of CML from CP to AP and AP to BC in early phase before terminal blast crisis phase is very important. The mechanism that leads to disease progression is not exactly known. There are many possible Genetic and Epigenetic Mechanism that leads to CML progression. Promoter hypermethylation is one of the possible epigenetic mechanisms that leads to inactivation of tumor suppressor gene in hematological malignancies. GADD45G is one of the tumor suppressor gene among panel of tumor suppressor genes involved in cancers especially hematologic...
Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a ... more Aim: To review the role of vitamin D in COVID-19. Background: The COVID-19 pandemic has caused a tremendous social and economic impact worldwide, and rapid outspreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being seen in India. Currently, there are two explanations available for the fatal ARDS in COVID-19 cases. Cytokine storm is characterized by unregulated release of various proinflammatory cytokines, i.e., TNF-α, INF-γ, IL2, IL6, IL8, IL12, CCL2, CCL3, and CXCL10, after interaction between SARS-CoV-2 and host immune cells. On the other hand, bradykinin storm is happening due to downregulation of ACE in the lung tissue. Immunomodulatory effects of vitamin D is proved through various studies. There is no individual therapy and vaccination for the SARS-Cov-2; thus, repurposing of available medicines is crucial now. Antiviral, anti-inflammatory, and immuno-boosting effects of vitamin D has proven in many studies. These effects are very relevant for its putative beneficial effect in SARS-CoV-2. Review result: Vitamin D has already been used as a repurposed drug in H5N1 pneumonia. Immunomodulatory and antibacterial role of vitamin D is well established. There are studies suggesting toward the cytokine storm as a main culprit behind deadly ARDS in COVID-19. Vitamin D was found as an anti-inflammatory and lung protective substance. Vitamin D was also found protective against bacterial LPS-induced injury by increasing expression of ACE-II and producing antibacterial protein cathelicidin. Conclusion: Before COVID-19 pandemic, we realized the silent pandemic of vitamin D deficiency. The immunomodulatory, anti-inflammatory, and antibacterial role of vitamin D has been shown in many studies. There are studies which have demonstrated the inverse relationship between vitamin D level and susceptibility to COVID-19. Vitamin-D also plays a crucial role in limiting the fibrosis in the damaged pulmonary tissue and also responsible for deciding overall morbidity of the patient. Thus, it is imperative to think about the potential of vitamin D as a repurposed drug for COVID-19 cases.
MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a... more MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a therapeutic target in various cancers. In this study, we analyzed alterations in the expression of miR-486-5p in chronic Myeloid Leukemia (CML) patients. Initially, the expression of miR-486-5p was studied in the BCR-ABL1+ve CML K562 cell line by quantitative realtime polymerase chain reaction (qRT-PCR). The results indicated that the miR-486-5p expression was significantly upregulated in K562 cells after imatinib exposure, as compared to untreated K562 cells (p-value = 0.047). These observations were corroborated by a hospital-based study of the miR-486-5p expression in peripheral blood leucocytes of 36 CML patients in the chronic phase (CP) and compared with age and sex-matched healthy volunteers as control subjects. qRT-PCR-based quantification revealed significant downregulation of the miR-486-5p expression in newly diagnosed untreated CP-CML patients' samples (2 −ΔCt = 13.19 ± 14.41) as compared to control samples (2 −ΔCt = 254.5 ± 274.8) (p-value < 0.0001). Levels of miR-486-5p were found to be distinctly elevated in the post-imatinib treatment samples of CML patients (2 −ΔCt = 469.7 ± 312.9) as compared to pre-treatment samples (p-value < 0.0001). CML patients' clinical and hematological responses to imatinib therapy (oral dose of 400 mg OD) were monitored for 12 months. The correlation of pre-treatment miR-486-5p levels with Sokal score indicated that patients with a higher expression of miR-486-5p had better prognoses. Patients with higher pre-imatinib miR-486-5p levels also showed a major hematologic response to imatinib in a shorter time and vice versa. To the best of our knowledge, this is the first report of alterations in the miR-486-5p expression in peripheral blood leucocytes of CML patients. Our observations support a tumor suppressor role of miR-486-5p in CML. The downregulation of the miR-486-5p expression may be critically important in the disease progression of CML patients. The upregulation of the miR-486-5p expression in post-imatinib exposure K562 cells and CML patients after 12 months of imatinib treatment suggests an onco-suppressor effector role of miR-486-5p in the BCR-ABL downstream signaling pathway. miR-486-5p can be explored as a novel biomarker for the early detection of CML.
Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approxima... more Introduction: Epilepsy is the most common heterogeneous neurological disorder affecting approximately 42 million people worldwide. Juvenile myoclonic epilepsy (JME) is a common form of idiopathic generalized epilepsy representing 5-10% of all epilepsy cases. Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood onset, the cause of which may be symptomatic, i.e., secondary to an underlying brain disorder or cryptogenic, i.e., with no known cause. Sodium channels are integral membrane proteins which play a central role in neuronal membrane excitability and action potential generation. Alpha subunit of voltage gated sodium channels encoded by SCN1A, SCN2A and other genes is pivotal for neuronal signalling. It was planned to analyse the roles of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms in the pathophysiology and risk JME and LGS in the Indian population. Methods: A total of 50 JME patients, 50 LGS Patients and 100 age and sex matched healthy volunteers were recruited in this study. The genotyping of SCN1A Thr1067Ala i.e., 3184 A>G (rs2298771) and SCN2A Arg19Lys i.e., 56 G>A (rs17183814) polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The SCN1A Thr1067Ala polymorphism genotypic distribution in LGS was significantly different from the normal population (P=0.008), with mutant homozygous (GG) plus heterozygous (AG) genotypes' percentage in LGS patients (16%) being lower than in healthy controls (24%). Frequency of the mutant 'G' allele of this SNP in LGS patients was 0.1, while it was 0.2 in control subjects (P=0.04). These observations which suggest a protective role of SCN1A Thr1067Ala polymorphism in LGS, were in sync with computation of an odds ratio of 0.21 (95% CI 0.07 to 0.66, p=0.005) for the GG genotype in LGS patients. Though no correlation of SCN1A Thr1067Ala SNP with the severity of disease phenotype in LGS viz. frequency/duration of seizures etc. was noted, a conflicting finding was the significant association of its mutant genotypes with an early age of onset of the syndrome (p=0.007). Contrary to the findings in SCN1A Thr1067Ala, in case of SCN2A Arg19Lys polymorphism, though a significantly different genotypic distribution was present in LGS, in comparison to normal population (p=0.03), the mutant homozygous (AA) and heterozygous (GA) combined percentage in LGS patients (16%) was greater than in healthy controls (11%). This was complemented by observation of an odds ratio of 4.24 (95% CI 1.15 to 15.55, p=0.029, in case of LGS patients with heterozygous (GA) genotype, indicative of an increased disease susceptibility. Unlike LGS, in JME patients no significant differences in genotypic/allelic frequencies of SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms were noted and the associated odds ratios for mutant genotypes were also non-significant. Conclusion: The SCN1A Thr1067Ala and SCN2A Arg19Lys polymorphisms may play contrary roles in the pathophysiology of LGS. Inheritance of SCN1A Thr1067Ala mutant allele decreases the susceptibility for LGS occurrence, and may hamper Na + channels opening and neuronal excitability. On the other hand, the mutant allele of SCN2A Arg19Lys polymorphism confers an increased risk for development of LGS, consequent to a likely facilitatory effect on action potential generation and misfiring in neurons. Neither of these two SNPs appears to influence the pathogenesis/susceptibility to JME.
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