Yousra Sediri

Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ-2 gene on obesity risk and leptin levels in a Tunisian population

OBJECTIVES This study was undertaken to investigate the impact of the Pro12Ala (rs1801282) polymorphism of the peroxisome proliferator-activated receptor gamma-2 (PPARgamma-2) gene on obesity or body mass index (BMI) and plasma leptin, insulin, adiponectin and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS The study included 387 obese patients and 288 control subjects. The Pro12Ala genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease BstUI. RESULTS In the whole population, there is no significant difference in genotype frequencies of the Pro12Ala polymorphism between obese patients and controls. However, separate analysis by gender revealed that obese men (but not women) had significantly higher frequency of Pro/Ala genotypes compared to controls (12.2% vs. 4.1%; chi(2)=6.76, p=0.009). In comparison to Pro/Pro homozygotes, Ala-allele bearers had a significantly higher risk of obesity [OR (95% CI)=3.26 (1.28-8.33)]. When obese subjects were stratified according to type 2 diabetes status, the association with obesity was only significant in obese non-diabetic patients [OR (95% CI)=3.74 (1.43-9.74), p=0.007]. Additionally, obese male patients carrying the Ala-allele had significantly higher body mass index (p=0.007) and plasma leptin levels (p=0.023) compared to those homozygous for Pro-allele. The significant effect of Pro12Ala polymorphism on plasma leptin levels disappeared after adjustment for age and BMI. CONCLUSION The present study provides evidence that the Pro12Ala polymorphism of the PPARgamma-2 gene is associated with obesity in non-diabetic men from Tunisian origin.

Association of G-2548A LEP polymorphism with plasma leptin levels in Tunisian obese patients.

OBJECTIVES The aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population. DESIGN AND METHODS Two hundred and twenty nine obese patients (BMI>or=30 kg/m(2)) were screened and compared to 251 normal weight subjects (BMI<25 kg/m(2)). The human leptin gene promoter G-2548A genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease CfoI. RESULTS In the entire study sample, carriers of -2548A allele had significantly lower leptin levels than homozygous for -2548G allele (14.28+/-9.10 ng/mL vs. 18.27+/-12 ng/mL, p<0.001 respectively) adjusted for BMI and gender. In obese patients but not control, subjects carrying the -2548A allele exhibited lower leptin levels than those with GG genotype (16.96+/-8.27 ng/mL vs. 21.37+/-11.72 ng/mL, p=0.001 respectively) adjusted for BMI and gender. In this group, carriership of the -2548A allele was identified, by multiple linear regression models, as significant independent predictor for leptin levels variability. Separate analyses by gender revealed that only in obese women, the -2548A allele was found to be associated with lower leptin levels independently of BMI (p=0.004). CONCLUSIONS The present study showed that G-2548A LEP polymorphism is associated with lower leptin levels in Tunisian obese women.

LEPR p.Q223R Polymorphism Influences Plasma Leptin Levels and Body Mass Index in Tunisian Obese Patients

BACKGROUND AND AIMS The leptin receptor (LEPR) plays a crucial role in the regulation of body weight. Several common polymorphisms have been described in the human LEPR gene including the p.Q223R polymorphism (rs1137101). The association of this polymorphism with obesity or related metabolic phenotypes has been controversial. The aim of this study was to investigate the impact of the LEPR p.Q223R polymorphism on body mass index (BMI), plasma leptin and lipid parameters in a sample of the Tunisian population. METHODS The study included 391 obese patients and 302 normal weight subjects. LEPR p.Q223R genotypes were identified by the PCR-RFLP analysis. RESULTS Obese patients homozygous for RR genotype showed lower leptin levels than those with other genotypes (p = 0.005) adjusted for age, BMI and gender. Stratified analysis by gender revealed that obese male patients carrying the R allele showed significantly lower BMI (p = 0.007) and leptin levels (p = 0.037) than subjects homozygous for the Q allele. In obese women, the LEPR p.Q223R polymorphism was found associated with lower leptin concentrations (p = 0.05). After adjustment for age and BMI, the association between the LEPR variant and plasma leptin remained significant only within female patients (p = 0.027). A general linear model including leptin as dependant variable and age, BMI, menopausal status and genotype as covariates revealed that the LEPR p.Q223R polymorphism is independently associated with leptin levels in obese women (p = 0.026). CONCLUSIONS Our findings suggest that the LEPR p.Q223R polymorphism influences plasma leptin levels and BMI in obese patients.

The paraoxonase L55M and Q192R gene polymorphisms and myocardial infarction in a Tunisian population.

OBJECTIVES In the present study, we examined a possible association between the PON1 Q192R and L55M polymorphisms and myocardial infarction (MI) in a sample of the Tunisian population. DESIGN AND METHODS Three hundred and ten patients with MI and 375 controls were recruited. Paraoxonase gene polymorphisms at codon 192 and 55 were analyzed by PCR-RFLP. RESULTS Genotype distributions and allele frequencies of L55M were similar among the control and MI groups. For the Q192R polymorphism patients with MI had significantly higher frequency of the RR genotype compared to controls [17.1% vs. 10.9%; OR (95% CI), 1.93 (1.24-3.02); p=0.004]. The MI patient group showed a significantly higher frequency of the R allele compared to the controls [38% vs. 30%; χ(2)=10.74, p=0.001]. The association between the PON1 Q192R polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors. CONCLUSIONS The present study showed a significant and independent association between the PON1 Q192R polymorphism (presence of R allele) and MI in the Tunisian population.

The ‐2548G/A LEP polymorphism is associated with blood pressure in Tunisian obese patients

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 (p = 0.003) and diastolic (p = 0.002) 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 (p = 0.01) and diastolic (p<0.001) 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 (p = 0.03). Conclusion. The present study showed that the ‐2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

Association between -786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population

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.

Association of a DNA polymorphism of the apolipoprotein AI-CIII-AIV gene cluster with myocardial infarction in a Tunisian population

BACKGROUND Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and high-density 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 reaction--restriction 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 (co-dominant 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.

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.

Association of rs2781666 G/T polymorphism of arginase I gene with myocardial infarction in Tunisian male population

OBJECTIVES The aim of this study was to investigate the association between rs2781666 G/T polymorphism of arginase I (ARG I) gene and myocardial infarction (MI) in the Tunisian male population. DESIGN AND METHODS Three hundred eighteen patients with MI and 282 controls were recruited. The rs2781666 G/T polymorphism of ARG I was determined by PCR-RFLP analysis. RESULTS Patients had significantly higher frequency of TT genotype compared to controls (10.4% vs. 6.7%; p<0.001). The MI patients showed higher frequency of T allele compared to the controls [0.33 vs. 0.22; OR (95% CI), 1.79 (1.37-2.34), p<0.001]. The association between rs2781666 G/T polymorphism of ARG I gene and MI remained significant after adjustment for other well-established risk factors. CONCLUSION A significant association between rs2781666 G/T polymorphism of ARG I gene and MI was found in the Tunisian male population.

The G3057A LEPR polymorphism is associated with obesity in Tunisian women

OBJECTIVES The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; χ(2)=4.90, p=0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA+AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; χ(2)=4.08, p=0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR=2.73, 95% CI 1.03-7.21) and for carriers of GA+AA genotypes (OR=1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations. CONCLUSION There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women.