The association between dietary vitamin K intake and serum undercarboxylated osteocalcin is modulated by vitamin K epoxide reductase genotype

Vitamin K acts as a cofactor during the gamma-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18-81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83-4/37.6 mu g/d in men and 79-6/29-8 mu g/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iCC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1 + 2255 genotype revealed that only in carriers of the GG genotype (39% of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene.