Association Study of Polymorphic Variants in 9P21 Locus and the Manifestation of Coronary Artery Disease in Bulgarians

Abstract Objective The variant 9p21 is correlated with coronary artery disease (CAD) in multiple studies in the European population, but we lack information for the Eastern Europeans (Caucasian). We aimed at investigating the potential association of six common polymorphic variants in 9p21 locus (rs7865618, rs1537378, rs7857345, rs10757274, rs2383206, and rs10757278) with CAD in the Bulgarian population. Materials and methods The current analysis included 261 patients with angiographically documented CAD (153 with myocardial infarction and 108 without myocardial infarction) and 496 population controls. Genomic DNA was isolated from peripheral venous blood. The selected polymorphic variants in 9p21 locus were genotyped by high resolution melting (HRM) analyses (Rotor Gene, Qiagen). Allelic and genotypic frequencies for studied variants were compared between cases and controls using the X 2 test. Results No deviation from the Hardy-Weinberg was observed for all polymorphic variants in both patient’ and control’ groups (p > 0.05). Polymorphic allele A for rs7865618 was found to be higher in the patient group than in the population controls (65.08% vs 58.28%). The carrier of this allele poses a 1.4-fold higher risk of myocardial infarction development than wild-type alleles‘ carriers (OR 1.40 (A) CI 1.04-1.70, p = 0.019), and this dependence is not related with gender. In female, an association between the allele C of rs7857345 and a 1.64-fold increased risk of myocardial infarction was observed (OR 1.64, CI95: 1.03-2.61, p = 0.03). For the other studied polymorphisms, no statistically significant association with disease risk was found. Also, our study found a positive association between rs2383206 and decreased serum triglyceride levels and with serum level of LDL cholesterol. Conclusion Further studies with a larger number of cases and controls will be needed in order to evaluate the possible association between the six studied polymorphisms and CAD/MI in Bulgarians.