Faculté De Médecine De Tunis

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The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.

Objective. To examine the association of a common -2548G/A (rs7799039) promoter variant of the human leptin gene (LEP) with obesity or body mass index (BMI) and its associated phenotypes such as blood pressure variability and the prevalence of hypertension in a sample of the Tunisian population. Design and methods. Two hundred and twenty-nine obese patients were screened and compared with 251 normal weight subjects. The -2548G/A LEP polymorphism was analysed by PCR-RFLP procedure. Results. No significant association was found between the -2548G/A polymorphism and obesity or BMI. However, in obese patients subjects with AA genotype had significantly higher systolic (p50.003) and diastolic (p50.002) blood pressure compared with those with GA or GG genotypes. Stratified analysis by gender revealed that male patients but not female homozygous for -2548A allele exhibited significantly increased systolic (p50.01) and diastolic (pv0.001) blood pressure than did carriers of -2548G allele. Multiple linear regression analysis revealed that AA genotype significantly affect systolic and diastolic blood pressure in obese men. Additionally, significant association between AA genotype and higher prevalence of hypertension was found in male patients (p50.03). Conclusion. The present study showed that the -2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

Background: Elevated plasma total homocysteine (tHcy), a risk factor for coronary artery disease (CAD), is due to defects in genes encoding for enzymes involved in tHcy metabolism or from inadequate status of vitamins involved in tHcy disposal. Methionine synthase (MS), a vitamin B 12 -dependent enzyme catalyses the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetrahydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter tHcy as well as folate levels which are independent risk factors for CAD. The influence of a common genetic polymorphism 2756A)G of the MS gene (MTR) on plasma tHcy, folate and vitamin B 12 (vit B 12 ) levels and its relation to the risk of myocardial infarction (MI) in a Tunisian case-control study was investigated. Methods: A total of 321 Tunisian patients with MI and 343 healthy controls were included in the study. The 2756A)G variant of the MTR was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Plasma tHcy was assessed with a fluorescent polarising immunoassay method. Plasma vit B 12 and folate were determined by microparticular enzyme immunoassay and ion-capture, respectively. Results: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 1.9% for the GG genotype, 26.2% for the AG genotype and 72% for the AA genotype. The controls had a frequency of only 0.9% for the GG genotype, 18.7% for the AG genotype and 80.5% for the AA genotype (x 2 s6.97, ps0.03). The MI patient group showed a significant higher frequency of the G allele compared to the controls (0.149 vs. 0.101; OR 1.55; 95% CI 1.10-2.18; ps0.008). The association between the 2756A)G variant in the gene encoding MS and MI was no longer significant after adjustment for other well-established risk factors. When clinical and laboratory values were compared amongst genotypes in the study groups, no significant differences were noted.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and education use, including for instruction at the author's institution, sharing with colleagues and providing to institution administration.

Background: Nitric oxide (NO) is produced by endothelial cells and serves as a potent vasodilator. Several lines of evidence have shown that NO plays an important role in the regulation of blood pressure and regional blood flow. Recent genetic studies have shown an association between the -786TC polymorphism in the endothelial nitric oxide synthase gene (NOS3) and coronary artery diseases, but any possible association with hypertension has been controversial. In the present study, we examined a possible association between the -786TC polymorphism of the NOS3 gene and hypertension in a sample of the Tunisian population. Methods: A total of 288 unrelated Tunisian patients with hypertension and 373 normotensive subjects were included in the study. The -786TC gene polymorphism was analyzed by PCR-RFLP. Results: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 19.7% for CC genotype, 52.9% for TC genotype and 27.3% for TT genotype. The control had a frequency of 14.7% for the CC genotype, 47.2% for the TC genotype and 38.1% for the TT genotype (χ² = 9.09, p = 0.01). The hypertension patient group showed a significant higher frequency of the C allele compared to the controls (0.46 vs. 0.38; χ² = 8.26, p = 0.004). The odds ratio of hypertension for C vs. T allele frequencies was statistically significant 1.59 (1.14-2.21) at 95% CI, p = 0.004 in men, whereas it was non-significant in women 1.21 (0.87-1.67), p =0.23. Conclusion: The present study showed a significant and independent association between the -786TC gene polymorphism (presence of C allele) and hypertension in the Tunisian population.

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3 ± 7.6 years) and 180 postmenopausal women (mean age 53.4 ± 6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDLcholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre-to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.

Résumé. L'apolipoprotéine B (Apo B) joue un rôle central dans le métabolisme des lipoprotéines et dans l'homéostasie du cholestérol. Plusieurs polymorphismes du gène de l'Apo B (XbaI, EcoRI, MspI) ont été décrits associés à des variations de concentrations lipidiques, à l'obésité et à la maladie coronarienne. À l'heure actuelle, il n'existe pas de données établissant la relation entre les paramètres lipidiques et les polymorphismes de l'Apo B dans une population tunisienne. Le but de notre travail était d'étudier les fréquences allèliques du polymorphisme XbaI du gène de l'Apo B dans une population tunisienne et d'évaluer le risque d'hyperlipidémie associé à ce gène dans cette population. Le génotypage de l'Apo B était déterminé par PCR-RFLP dans 296 échantillons sanguins provenant de Tunisiens recrutés dans la région du grand Tunis (112 femmes et 184 hommes, âgés de 51,4 ± 9,6 ans). Par ailleurs, le cholestérol total, les triglycérides, le HDL-cholestérol et les apolipoprotéines A1 et B ont été également mesurés. On observe un effet significatif du polymorphisme XbaI du gène l'apolipoprotéine B sur le cholestérol total (p = 0,04), les triglycérides totaux (p = 0,02) et l'apolipoprotéine A1 (p = 0,004), avec un ″ effet-dose ″ du gène (augmentation progressive des concentrations du groupe X1X1 au groupe X2X2, les patients hétérozygotes X1X2 ayant des valeurs intermédiaires). En fonction du sexe, l'effet du polymorphisme XbaI n'est observé que pour les triglycérides chez les hommes. Ces résultats mettent en évidence l'influence du polymorphisme XbaI du gène de l'Apo B sur les concentrations du cholestérol total, des triglycérides et de l'apolipoprotéine A1 dans une population tunisienne.

Although long term use of cyclooxygenase (COX)-2 inhibitors may be associated with increased cardiovascular risk, their effects on vascular reactivity in atherosclerosis has remained largely unexplored. The aim of the present study was to evaluate the role of COX-2 induced by an atherosclerotic process, in the local control of vascular tone. To this end, New Zealand White rabbits were fed 0.3% cholesterol for 3 weeks before being subjected to balloon injury of the abdominal aorta. After another 2 weeks, the aorta was removed and used for organ bath experiments and immunohistochemistry, and the prostaglandins released were measured using enzyme immunoassays. Hypercholesterolemia and vascular injury significantly increased the thickness of the intimal layer, which was associated with an induction of COX-2 immunoreactivity throughout the aortic wall. In these preparations, a significant decrease of the maximal contractions induced by norepinephrine was observed: 89.3±12 mN in controls (n=5) versus 67.6±13 mN in balloon injured aortas from hypercholesterolemic rabbits (n=5); P<0,05. The norepinephrine-induced contractions of atherosclerotic preparations were restored by the COX inhibitors DuP-697 (0.5 μmol/L) and indomethacin (1.7 μmol/L), to similar contractions as was observed in aortic preparations derived from healthy rabbits. Norepinephrine stimulation of the abdominal aorta was accompanied by increased levels of prostaglandin I 2 in atherosclerotic (1,39±0,11 μg/mg, n=3) compared with normal aorta (0,53±0,17 μg/ mg, n=3, P<0,05). Selective COX-2 inhibition significantly decreased the prostaglandin I 2 release from atherosclerotic aorta, but had no effect on the prostaglandin release from aortic preparations derived from normal rabbits. These observations suggest that the local induction of COX-2 during atherosclerosis decreased the sensitivity to norepinephrine, and that COX-2 inhibitors may locally increase vascular reactivity at sites of atherosclerotic lesions.

Background: Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and highdensity lipoprotein cholesterol. However, whether genetic variations in the ApoAI-CIII-AIV gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain. In the present study, we examined a possible association of the ApoCIII SacI polymorphism in the ApoAI-CIII-AIV gene cluster with lipid parameters and MI in a sample of the Tunisian population. Methods: A total of 326 Tunisian patients with MI and 361 controls were included in the study. Genotypes were determined by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) analysis. Results: A significant difference in genotype distribution and allele frequency was observed between patients and controls. At the multivariate analysis after adjustment for traditional vascular risk factors, the ApoCIII SacI polymorphism was significantly associated with MI, according to co-dominant and dominant models (codominant model odds ratio [OR]: 1.53, 95% confidence interval [CI]: 1.0-2.35, p = 0.04; dominant model OR: 2.02, 95% CI: 1.11-3.67, p = 0.02). The MI patient group showed a significant higher frequency of the S2 allele compared to the controls (10.2% vs. 6.5%; OR: 1.64, 95% CI: 1.10-2.47, p = 0.01). There was no statistically significant association between ApoAI-CIII-AIV cluster gene polymorphism and lipid, lipoprotein, and apolipoprotein levels in both MI patients and controls. Conclusion: In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.