Association Between the G20210A Polymorphism of Prothrombin Gene and Myocardial Infarction in Tunisian Population.

The prothrombin is the precursor of the serine protease thrombin, a key enzyme in homeostasis. Prothrombin G20210A polymorphism (rs1799963) was described as a moderate risk factor for venous thrombosis because this mutation is associated with prothrombin elevated levels which may lead to an imbalance between the procoagulant, anticoagulant, and fibrinolytic system. 20210A carriers have an increased risk of thrombosis. In this study, we proposed to determine the prevalence of 20210A prothrombin variant among Tunisian population, and to evaluate the potential relevance of this variant with myocardial infarction. This study included 1290 unrelated Tunisians (1007 male and 283 female) divided in two groups: Four hundred and eighty-seven MI patients (mean age: 52.64 ± 8.98 years) and 803 apparently healthy controls (mean age: 51 ± 8.99). The prothrombin G20210A polymorphism was carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. The distribution of genotypes was in accordance with Hardy-Weinberg equilibrium (p > 0.05). A significant difference in genotype distribution and allele frequency was observed between patients and controls. Male patients with MI had a frequency of 97 % for GG genotype and 3 % for GA+AA genotypes. The control group had a frequency of 99 % for the GG genotype and 1 % for the GA+AA genotypes which is significantly lower than the frequency found in patients (p = 0.01). The same genotype frequencies were found in women (p = 0.032). The MI patient group showed a significantly higher frequency of 20210A allele compared to controls 0.02 versus 0.01 [OR = 3.60 (95 % CI = 1.29-10.53), p = 0.005] in men and 0.015 versus 0.068 [OR = 4.68 (95 % CI = 1.60-14.26), p = 0.001] in women. Our work showed a significant but not independent association between the G20210A polymorphism of the prothrombin gene and MI in the Tunisian population.

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 between endothelial nitric oxide gene intron 4a4b VNTR polymorphism and plasma homocysteine concentrations in Tunisian male patients with myocardial infarction.

Many studies have shown that hyperhomocysteinemia may be an independent risk factor for coronary artery disease. However, not all prospective studies support an association between elevated plasma homocysteine levels and coronary artery disease. Nitric oxide (NO) plays a relevant role in various events during atherogenesis, and in vitro data suggest that NO may modulate total homocysteine (tHcy) concentrations, whereas polymorphisms of the endothelial nitric oxide (NOS3) gene have been reported to be related to an increased risk of myocardial infarction (MI) and hyperhomocysteinemia, but the results have been controversial. We hypothesized that the NOS3 synthase 4a4b VNTR polymorphism is a determinant of tHcy concentrations and tested this in 310 patients with MI and 250 controls. The NOS3 gene intron 4a4b VNTR polymorphism was analyzed by polymerase chain reaction analysis. There was no significant difference in the homocysteine levels between patients with MI and controls. The frequencies of the NOS34b4b, 4b4a, and 4a4a genotypes in the MI group were significantly different from those in the control group. In patients with MI, plasma tHcy concentrations were significantly different among the NOS3 genotypes (13.5±4.5, 18.5±3.9, and 20.4±2.1 µmol/L for 4b4b, 4a4b, and 4a4a genotypes, respectively; P<.001). However, no significant difference was observed for tHcy concentrations in the control group. In conclusion, the NOS34a4b gene polymorphism (presence of 4a allele) is associated with MI and influences plasma tHcy concentrations in patients with MI in the Tunisian male 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.

C(-260)T polymorphism in the promoter of CD 14 gene is not associated with myocardial infarction in the Tunisian population.

Recent findings suggest that inflammation plays a role in atherosclerosis and its acute complications. Several known mechanisms may play at least a partial role in this process. One of the most likely mechanisms involves lipopolysaccharide (LPS) and its receptor, CD14. The C(-260)T single nucleotide polymorphism (rs2569190) in the promoter region of the CD14 receptor gene has been reported to be associated with a higher risk of MI. Others studies, however, have not corroborated these findings. Considering the contradictory results, the aim of the present study was to investigate the possible association between the CD14 C(-260)T polymorphism and the risk of MI in the Tunisian population. A total of 321 Tunisian patients with MI and 344 healthy controls were included in the study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The frequency of TT homozygous genotype for the CD14 C(-260)T polymorphism was 26.2% in MI patients and 27.0% in the control group. However, the genotype distribution and allele frequencies were not significantly different between MI and controls subjects. Moreover, the odds ratio for MI associated with the TT genotype failed to reach statistical significance (OR=1.22; 95% CI: 0.85-1.77; p=0.272). These results do not support the hypothesis that the C-260T polymorphism of CD14 gene contributes to the genetic susceptibility to MI in the Tunisian population studied.

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.

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.

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.

Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-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.

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.

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.