G protein beta3 subunit gene C825T and angiotensin converting enzyme gene insertion/deletion polymorphisms in hypertensive Tunisian population.

BACKGROUND: We investigated the interaction between the G protein beta3 subunit (GNB3) C825T variant and angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism in hypertensive Tunisian population. METHODS: Analyses of ACE and GNB3 genotypes were performed in 388 hypertensive patients and 425 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The plasma ACE activity was determined by a spectrophotometric method. RESULTS: The ACE genotype distribution and allele frequencies were not significantly different between the hypertensive and normotensive subjects (p > 0.05). This polymorphism was not associated with hypertension (HTA) (OR = 0.93, 95% CI = 0.75 - 1.15; p = 0.50). In cases, subjects carrying the DD genotype exhibited higher plasma ACE activity than those with ID and II genotypes (p = 0.001). In this group, a linear regression analysis revealed that the ACE I/D polymorphism is independently associated with plasma ACE activity (p = 0.017). The genotypic distribution and allelic frequencies of the GNB3 C825T polymorphism were not significantly different between the two groups. This polymorphism was found to have no effect on the risk of HTA (OR = 1.14, 95% CI = 0.93 - 1.39; p = 0.21). We did not observe a significant interaction between the GNB3 gene and the ACE gene with HTA. CONCLUSIONS: In this study, the I/D polymorphism is a significant independent predictor for variability of plasma ACE activity but the ACE I/D and GNB3 C825T polymorphisms are not significant factors for HTA in the Tunisian population. Moreover, we found no interaction between ACE D allele and GNB3 825T allele solely or combined with respect to HTA 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 a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with hypertension in a Tunisian population.

OBJECTIVES: Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilatation and antithrombotic action. Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with hypertension have been reported. In the present study, we examined a possible association between the 27-base pair (bp) repeat polymorphism in intron 4 of the NOS3 gene and hypertension in a sample of the Tunisian population. DESIGN AND METHODS: A total of 295 Tunisian patients with hypertension and 395 healthy controls were included in the study. The NOS3 gene intron 4a4b variable number of tandem repeats polymorphism was analyzed by PCR. RESULTS: A significant differences in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 6.4% for the 4a4a genotype, 32.7% for the 4a4b genotype and 60.9% for the 4b4b genotype. The controls had a frequency of only 2.3% for the 4a4a genotype, 28.4% for the 4a4b genotype and 69.4% for the 4b4b genotype (chi(2)=11.81, p=0.003). The hypertension patient group showed a significant higher frequency of the 4a allele compared to the controls (0.23 vs. 0.16; chi(2)=8.61, p=0.003). The odds ratio of hypertension for 4a vs 4b allele frequencies was statistically significant 1.66 [1.09-2.53] at 95% CI, p=0.01 in males, whereas it was non-significant in females (1.23 [0.84-1.81], p=0.26). CONCLUSION: The present study showed a significant and independent association between the NOS34a4b gene polymorphism (presence of 4a allele) and hypertension in the Tunisian population.

Association between the 2756A> G variant in the gene encoding methionine synthase and myocardial infarction in Tunisian 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-methyltetra-hydrofolate, 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) 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 vitamin 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. 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 (chi(2)=6.97, p=0.03). The MI patient group showed a significant higher frequency of the G allele compared to controls (0.149 vs. 0.101; OR 1.55; 95% CI 1.10-2.18; p=0.008). 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. CONCLUSIONS: The present study showed a significant but not independent association between the 2756A>G polymorphism of the MTR (presence of G allele) and MI in the Tunisian population.

Association between the -2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and myocardial infarction in Tunisian patients.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1; gene name CCL2) has been suggested to play an important role in the initiation of atherosclerosis by recruiting monocytes to sites of injured endothelium. Recently, single nucleotide polymorphisms (SNPs) in the MCP-1 regulatory region have been identified. Controversial results regarding the association of the -2518G/A polymorphism of the MCP-1 gene with coronary artery disease (CAD) have been reported. In the present study, we examined a possible association between the -2518G/A polymorphism of the MCP-1 gene and myocardial infarction (MI) in a sample of the Tunisian population. METHODS: A total of 319 Tunisian patients with MI and 467 healthy controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Patients with MI had significantly higher frequency of the AG+GG genotypes compared to controls [42.9% vs. 35.8%; OR (95%CI), 1.34 (1.00-1.79); p=0.04]. The MI patient group showed a significant higher frequency of the G allele compared to the controls [0.242 vs. 0.195; OR (95%CI), 1.31(1.02-1.68), p=0.03]. The association between the -2518G/A polymorphism of the MCP-1 gene and MI was no longer significant after adjustment for other well-established risk factors. CONCLUSION: The present study showed a significant but not independent association between the -2518G/A polymorphism of the MCP-1 gene (presence of G allele) and MI in the Tunisian population.