Association of VKORC1 −1639 G > A polymorphism with carotid intima–media thickness in type 2 diabetes mellitus

Abstract Aims Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1 , can lead to calcification. We examined a potential association between VKORC1 −1639 G > A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima–media thickness (cIMT). Methods VKORC1 −1639 G > A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR–RFLP. cIMT was measured in a subgroup of 118 T2DM patients. Results The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly ( p = 0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p = 0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 −1639 G > A polymorphism was an independent predictor of cIMT ( p = 0.029) after adjusting for established risk factors. Conclusions The association between VKORC1 −1639 G > A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 −1639 G > A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.