Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylase genes with biochemical measures of vitamin K status.

Author(s): Crosier MD, Peter I, Booth SL, Bennett G, Dawson-Hughes B, Ordovas JM

Affiliation(s): USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.

Publication date & source: 2009-04, J Nutr Sci Vitaminol (Tokyo)., 55(2):112-9.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity may be explained by differences in vitamin K status. Men and women (n=416, 60-80 y), primarily of European descent, were genotyped for common polymorphisms in VKORC1 and GGCX. Cross-sectional associations exist between polymorphisms and biochemical markers of vitamin K [plasma phylloquinone, percent undercarboxylated osteocalcin (%ucOC)]. VKORC1 rs8050894 GG homozygotes had significantly higher cross-sectional measures of plasma phylloquinone than carriers of the CG or CC genotypes (plasma phylloquinone geometric means: GG 0.874+/-0.092 versus CG/CC 0.598+/- 0.044; p=0.020), whereas carriers of VKORC1 rs7294 AA or AG had significantly lower plasma phylloquinone concentrations compared to GG homozygotes (plasma phylloquinone geometric means: 0.579+/-0.045 versus 0.762+/-0.057; p=0.035). Cross-sectional analyses also revealed that heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower %ucOC relative to either homozygous group. Polymorphisms in genes encoding enzymes involved in vitamin K metabolism may modulate plasma concentrations of phylloquionone and percent carboxylation of osteocalcin.