Genetic variation in cyclin dependent kinase inhibitor 2A/2B(CDKN2A/B) is associated with the risk of coronary artery disease in Chinese type 2 diabetes

Objective To investigate the association of eyclin dependent kinase inhibitor 2A/2B (CDKN2A/B) polymorphisms with the risk of coronary artery disease in type 2 diabetics in China. Methods Of total 309 subjects with type 2 diabetes,220 individuals with coronary artery disease as cases (CAD) and 89 controls (Non-CAD)were studied. From the Hapmap CHB database, we selected 7 haplotype-tagging single nucleotide polymorphisms(SNPs) in CDKN2A/B genes: CDKN2A rs2811708 (G T), rs3088440(AG)and rs3731239(CT);CDKN2B rs3217986(AC),rs1063192(CT), rs2285327 (AG)and rs3217992(AG). All the subjects for the 7 SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)assay or by direct DNA-sequencing. Results In Chinese type 2 diabetic patients, allelic frequency of minor allele T at rs2811708 was higher in CAD group(26.4%)than in non-CAD group(17.4%)(OR=1.698, 95%CI 1.092～2.640, P=0.019). Genotypic frequency at rs2811708 was associated with the risk of CAD in type 2 diabetics(P=0.028). The carriers of genotype G/T had the increased risk of CAD compared to those of genotype G/G(OR= 2.074, 95%CI 1.194～3.601,P=0.010), and the association was consistent after adjustment for the other known risk factors of cardiovascular disease (adjusted OR′=2.503,95% CI 1.298～4.825, P′= 0.006). Conclusions Genetic variation in cyclin dependent kinase inhibitor 2A/2B(CDKN2A/B)genes is associated with cardiovascular risk in Chinese type 2 diabetics.