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 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

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

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