Vitamin K epoxide reductase complex, subunit 1

The translation product of the VKORC1 gene is involved in vitamin K activation. While some mutations cause a combined deficiency of vitamin-K dependent coagulation factors, polymorphisms in this gene's coding region and its promotor have been associated with decreased response or increased sensitivity to vitamin K antagonists.

Epidemiology

The G allele at position -1639 is more common in Caucasian while the A allel is more frequent in Chinese, which fully explains differences in warfarin susceptibility among these two populations. Some other more downstream polymorphisms, that also have been associated with varying therapeutic doses of vitamin K antagonists, appear to be in linkage disequilibrium.

Gene Structure

The gene spans 4,1kb on chromosome 16 (16p11.2). The two splice variants consist of up to 3 exons. The promotor contains an E-Box at position -1644. A single nucleotide polymorphism, -1639G>A is located in the E-Box' consensus sequence (CANNTG). In various experiments, it could be demonstrated that the -1639G allele is associated with a more prominent expression of the gene, which ensues increased vitamin K activation and restraint effect of vitamin K antagonists.

Genetests:

Related Diseases:

Combined deficiency of vitamin K-dependent clotting factors type 2
	VKORC1

Coumarin resistance
	CYP2A6
	CYP2C9
	CYP4F2
	VKORC1