Influence of VK0RC1 Haplotypes on Cardiovascular Disease

摘要

Coronary heart disease is one of the leading causes of morbidity and mortality in Europe. Atherogenesis and vascular calcification have been linked to vitamin K and the downstream pathways of vitamin K dependant proteins acting in blood coagulation and calcium metabolism. All these proteins only reach full biological activity by sufficient gamma-carboxylation requiring vitamin K hydroquinone. Resulting vitamin K epoxide is recycled to active hydroquinone by vitamin K epoxide reductase complex subunit 1 (VK0RC1). Shortly after cloning of this key enzyme of vitamin K recycling, gene haplotype VKORC1*2 was shown to have a substantial impact on VK0RC1 mRNA transcription rate lowering promoter activity by approximately 50%. Most recently, non VKORC1*2 alleles have been reported to represent a major risk factor for coronary heart disease, stroke, and aortic dissection in Chinese patients.