Polymorphisms of the 11q23.3 Locus Affect the Risk and Mortality of Coronary Artery Disease.

Background: The present study aimed to determine whether the polymorphisms of the 11q23.3 locus affect the risk and mortality of coronary artery disease in 5-year and 10-year observations. Methods: The study group consisted of 519 subjects: 276 patients with CAD and 243 blood donors as controls. The genotyping of polymorphisms (rs10750097, rs3741298, and rs1729410) was performed using the TaqMan-PCR method. Survival was defined as the period from the angiographic confirmation of CAD to cardiovascular death, and the endpoint was defined as death from cardiovascular causes. Results: The G allele of the rs1729410 polymorphism increased the risk of CAD (OR = 1.55, p = 0.04) and showed a synergistic correlation with overweight/obesity (additive synergy index (SI) = 11.01, p < 0.001). The carriers of the GG genotype and over-normative LDL levels increased the risk of CAD by over 12-fold higher than expected (multiplicative synergy index (SIM) = 12.34, p < 0.001). In the case of the rs10750097 variant, an effect on mortality was shown in both 5-year and 10-year periods. Conclusion: The results revealed that the rs1729410 polymorphism increases the risk of CAD in synergy with traditional risk factors, and the rs10750097 polymorphism of the 11q23.3 locus affects the risk of death in patients with CAD.

The relationship between CYP7A1 polymorphisms, coronary artery disease & serum lipid markers.

Polymorphic variants of the CYP7A1 gene can increase the risk of atherosclerosis-based coronary artery disease (CAD) and modify serum lipid markers. Method: We studied haplotype-tagging single nucleotide polymorphisms of CYP7A1 in the Caucasian population and if they are associated with CAD, its symptoms, and any of its risk factors. Results: We did not find the genetic variants of CYP7A1 to be associated with an increased risk of CAD. However, we did find that the common rs3808607 variant is associated with modified concentrations of serum total cholesterol and LDL. We also found that the C allele and the CC genotype of the rs11786580 are more frequent in patients with myocardial infarction. This association was especially strong after the group differentiation by sex.

Analysis of selected promoter polymorphisms and haplotypes of the CYBA gene encoding the p22phox, subunit of NADPH oxidases, in patients with coronary artery disease.

The p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA gene. It was shown that functionally relevant polymorphisms of the CYBA gene -930A > G, -852C > G, -675A > T, -536C > T, 214C > T (previously described as 242C > T), *24A > G (previously described as 640A > G), and *49A > G modulate generation of reactive oxygen species (ROS). To analyse whether the CYBA gene polymorphisms -852C > G, -675A > T, and -536C > T were associated with coronary artery disease (CAD), and to designate haplotype blocks. Four hundred and ninety subjects: 245 patients with CAD and 245 age and sex-matched controls. The polymorphisms were genotyped using the PCR-RFLP method and the TagMan® Pre-designed SNP Genotyping Assay. The analysed polymorphisms do not form haplotype blocks. Case-control study revealed that the -930 G/-675T and -930G/*49G diplotypes were a CAD risk factor. The 675T/*49G diplotype can modulate CAD risk in women. The protective effect reducing CAD risk in women was related to the -930A/-675T and -930A/*49A diplotypes. Carrier state of the -852C allele (-852C > G) was associated with multivessel stenosis while the CC genotype of the -536C > T polymorphism was more frequent in patients with peripheral artery disease. Hypercholesterolemic, cigarette smokers had an increased risk of CAD, especially C - 852 allele (-852C > G) carriers (SIM = 3.54; odds ratios (OR) = 10.01, p < 0.000). The CYBA gene polymorphisms modulate the risk of CAD but do not form a haplotype blocks.

Relationship between CETP gene polymorphisms with coronary artery disease in Polish population.

The cholesteryl ester transfer protein (CETP) gene encodes a hydrophobic glycoprotein that plays a crucial role in the reverse transport of cholesterol. The aim of the present study was to determine whether CETP polymorphisms (rs1532624, rs247616 and rs708272) are associated with coronary artery disease (CAD) in a Polish population. Serum lipid levels and single nucleotide polymorphisms of CETP genes were determined in 494 subjects: 248 patients with premature CAD and 246 blood donors as controls. Selected polymorphisms were examined using TaqMan PCR analysis. We found that CAD risk was significantly higher for CC homozygotes and C allele carriers of the rs247616 polymorphism than for carriers with the T allele (OR 1.89, 95% CI 1.29-2.76, p = 0.001 and OR 1.51, 95% CI 1.14-1.99, p = 0.003) and likewise for the CC genotype of the rs1532624 polymorphism than for those with the A allele (OR 1.59, 95% CI 1.05-2.40, p = 0.026). Moreover, T allele carriers of the rs708272 polymorphism had significantly higher total cholesterol levels compared to CC homozygotes (p < 0.05) in the healthy controls. We also observed an allelic pattern, C(rs2477616)C(rs708272)C(rs1532624), which increased susceptibility to CAD by 43% (OR = 1.43, 95% CI 1.10-1.85, p = 0.006). In conclusion, the rs247616 and rs1532624 polymorphisms of CETP may modulate the risk of CAD in Polish population.

Relationship between rs854560 PON1 Gene Polymorphism and Tobacco Smoking with Coronary Artery Disease.

Paraoxonase-1 (PON1) is the antioxidant marker of high-density lipoproteins protecting against atherosclerosis and coronary artery disease (CAD) phenotype. The purpose of the present study was to determine whether the PON1 gene rs854560 polymorphism (163T>A) is associated with CAD in Polish population. rs854560 was genotyped in 494 subjects: 248 patients with premature CAD and 246 blood donors as a control. We found that the risk of CAD was significantly higher in TT homozygotes than in A allele carriers (OR = 1.87, p = 0.041). The synergistic effect between the TT genotype and cigarette smoking was observed (SIM = 9.81; SI = 14.70). The relative increase in risk from interaction between factors was over 37 (RERI = 36.13). The PON1 polymorphism did not modulate the risk of CAD in response to exposure to other traditional risk factors. In conclusion, the rs854560 polymorphism may modulate the risk of CAD in response to cigarette smoking in Polish population. Carriers of TT genotype seem to be particularly at risk of CAD, when exposed to cigarette smoking.

The CYBA Gene (⁎)49A>G Polymorphism (rs7195830) Is Associated with Hypertension in Patients with Coronary Artery Disease.

Purpose. Single nucleotide polymorphisms of the CYBA gene may modify the risk of coronary artery disease (CAD). The aim of the present study was to investigate whether the (⁎)49A>G (rs7195830) polymorphism is associated with CAD. Materials and Methods. CYBA gene (⁎)49A>G polymorphism was determined in 481 subjects: 242 patients with premature CAD and 239 age and sex matched controls using the fluorescently labeled allele-specific oligonucleotides method. Results. The frequency of the (⁎)49G allele carrier state was significantly higher in patients than in controls (84.8% versus 76.6%, resp., P = 0.020), as well as the frequency of the (⁎)49G allele (62.2% versus 54.0%, P = 0.009). Both factors were associated with CAD in the analyzed population (OR = 1.70, 95% CI: 1.04-2.76 for GG+AG versus AA and OR = 1.40, 95% CI: 1.08-1.83 for (⁎)49G versus (⁎)49A). Carrier state of the (⁎)49G allele was a stronger and independent risk factor for CAD among women (OR = 4.35, 95% CI: 1.50-13.20, P = 0.002), as well as the (⁎)49G allele (OR = 2.25, 95% CI: 1.34-3.77, P = 0.001). The (⁎)49G allele carrier state was also associated with left ventricular hypertrophy in patients with coronary artery disease (P = 0.015). Conclusion. The CYBA gene (⁎)49A>G polymorphism modifies the risk of coronary artery disease.

CYP7A1 gene polymorphism located in the 5' upstream region modifies the risk of coronary artery disease.

BACKGROUND: 7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic conversion pathway leading from cholesterol to bile acids synthesis, is encoded by CYP7A1 gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid levels and may be related to impaired lipid profile leading to coronary artery disease (CAD). The aim of the present study was to analyze the possible association between the rs7833904 CYP7A1 polymorphism and premature CAD. MATERIAL AND METHODS: Serum lipid levels and rs7833904 SNP were determined in 419 subjects: 200 patients with premature CAD and 219 age and sex matched controls. RESULTS: The A allele carrier state was associated with CAD (OR = 1.76, 95% CI; 1.14-2.71, P = 0.014). The effect was even stronger in the male subgroups (OR = 2.16, 95% CI; 1.28-3.65, P = 0.003). There was no effect in the females. Risk factors of CAD and clinical phenotype of atherosclerosis were not associated with genotype variants of the rs7833904 SNP. Lipid profiles also did not differ significantly between individual genotypes. CONCLUSION: The CYP7A1 rs7833904 polymorphism may modify the risk of CAD. This effect is especially strong in male subjects. The studied polymorphism does not significantly influence serum lipid levels, in the present study.

The -930A>G polymorphism of the CYBA gene is associated with premature coronary artery disease. A case-control study and gene-risk factors interactions.

Reactive oxygen species (ROS) are involved in the pathogenesis of atherosclerosis and coronary artery disease (CAD). NADPH oxidases are the main source of ROS in the vasculature. p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA (cytochrome b245 alpha) gene. The -930A>G CYBA polymorphism (rs9932581:A>G) modulates the activity of the CYBA promoter, and influences CYBA transcriptional activity. The aim of the present study was to analyze a possible association between the -930A>G polymorphism and CAD and to search for gene-traditional risk factors interactions. 480 subjects were studied: 240 patients with premature CAD, 240 age and sex matched blood donors. The -930A>G polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). The -930G allele carrier state was a risk factor for CAD (OR 2.03, 95% CI 1.21-3.44, P=0.007). A synergistic effect of the -930G allele with overweight/obesity (BMI≥25) and cigarette smoking was found. The estimated CAD risk for BMI≥25 and the -930G allele interaction was about 160% greater than that predicted by assuming additivity of the effects, and about 40% greater for interaction of cigarette smoking and the -930G allele. Overweight/obesity was a risk factor for CAD only in the -930G allele carriers (P<10(-10)) but not in the AA homozygotes (P=1.00). In conclusion the -930A>G CYBA polymorphism is associated with CAD in the Polish population. The -930G allele carriers are particularly at risk of consequences of obesity and tobacco smoke exposure.