Functional promoter polymorphism in the VKORCI gene is no major genetic determinant for coronary heart disease in Northern Germans

Recently, the C-allele of polymorphism rs2359612 (VKORCI: c.283+837C > T) in the VKORCI gene has been reported to represent a major risk factor for coronary heart disease (CHD), stroke, and aortic dissection in Chinese patients.VKOR activity itself is the rate-limiting step in gamma-carboxylation of vitamin K-dependent coagulation factors (factors II,VII, IX, X, protein C, S, and Z) and proteins of calcium metabolism (matrix Gla protein and osteocalcin). Gamma-carboxylation is essential for the biological activity of these proteins that have been previously hypothesised to play a role in the pathogenesis of atherosclerosis. It was the objective of this study to analyse the VKORCI genotype frequency in patients with CHID and controls from Northern Germany and to investigate the association of VKORC11 and CHID risk in patients with an European background. CHID patients (n = 901) and healthy controls (n = 52 1) were part of the PopGen biobank. Case and control samples were matched for ethnic and geographic origin, age and gender.After typing German CHID patients and control individuals, no evidence for a statistically significant association was detected between VKORC1 genotype and CHD phenotype.Also, stratification for gender and myocardial infarction yielded no significant results. In conclusion, the discrepant association findings in Chinese and German populations may be explained by ethnic differences in genetic and perhaps environmental predisposition, modifying the polygenic CHD phenotype by interacting with VKORC1 variants and thus conferring disease susceptibility in some populations, but not in others.