Vitamin K epoxide reductase (VKORC1) gene mutations in osteoporosis: A pilot study

Translational Research : the Journal of Laboratory and Clinical Medicine
Gerold HolzerChristine Mannhalter

Abstract

Susceptibility to osteoporosis seems to be influenced genetically. Previous studies on the effects of genetic polymorphisms on bone mineral density (BMD) showed controversial results. Vitamin K hydrochinon is an important cofactor for gamma carboxylation of osteocalcin. The reduction of vitamin K to vitamin K hydrochinon depends on the vitamin K epoxide reductase complex subunit 1 (VKORC1). We evaluated the impact of polymorphisms in VKORC1 on BMD and fractures. In this single-center study, 184 individuals (141 female subjects and 43 male subjects, mean age: 63.2 +/- 14.3 years) were recruited. In all, 149 of 184 could be genotyped by allele-specific polymerase chain reaction (PCR) for the VKORC1 variants 3673G>A or 9041G>A. The genotypes were correlated with clinical parameters. Vitamin K(1) concentrations were determined by high-performance liquid chromatography (HPLC); carboxylated (GlaOC) and undercarboxylated osteocalcin (GluOC) was determined by enzyme-linked immunosorbent assays (ELISAs). The 9041 GG and GA genotypes were significantly more frequent in patients with low BMD (P = 0.012). Thus, carriers of at least 1 G-allele seem to have a higher risk for low BMD. No statistically significant association was found for the...Continue Reading

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