The C-565T Polymorphism (rs2422493) of the ATP-binding Cassette Transporter A1 Gene Contributes to the Development and Severity of Coronary Artery Disease in an Iranian Population.

ABSTRACT

OBJECTIVES: ATP-binding cassette transporter A1 (ABCA1) plays a pivotal role in reverse cholesterol transport from peripheral tissues back to the liver. Abnormalities in ABCA1 function may lead to dyslipidemia and coronary artery disease (CAD). We investigated the role of C-565T (rs2422493) promoter polymorphism of ABCA1 gene in the development and severity of CAD in an Iranian subpopulation. METHODS: Our study population consisted of 110 angiographically-confirmed CAD patients and 110 matched controls. The severity of CAD was expressed based on the number of stenotic vessels. Genotyping of C-565T promoter polymorphism was performed using the polymerase chain reaction followed by restriction fragments length polymorphism analysis methods. Lipid profile was determined by routine colorimetric methods. RESULTS: The distribution of ABCA1 C-565T genotypes (p = 0.035) and alleles (p = 0.017) was significantly different between the CAD and control groups. In univariate analysis (with genotype CC as reference), the TT genotype was significantly associated with an increased risk of CAD (odds ratio = 3.83; 95% confidence interval 1.29-11.30, p = 0.014), but the CT genotype was not (p = 0.321). A multiple binary logistic regression analysis revealed that smoking, hypertension, triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and ABCA1 C-565T dominant genotype were significant and independent risk factors for CAD development (p < 0.050). The ABCA1 C-565T polymorphism affected the severity of CAD in TT homozygote state (p = 0.028). However, no significant correlation was seen between this common polymorphism and lipid profile in the study population (p > 0.050). Conclusions: Our study indicated that ABCA1 C-565T polymorphism is a significant risk factor for development and severity of CAD in our population.