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Vitamin K epoxide reductase complex subunit 1 (Vkorc1) haplotype diversity in mouse priority strains

DOI: 10.1186/1756-0500-1-125

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Abstract:

In the commonly used laboratory strains of Mus musculus domesticus we identified only four haplotypes differing in the intron or 5' region sequence of the Vkorc1. Six haplotypes differing by coding and non-coding polymorphisms were identified in the other subspecies of Mus. We detected no significant association of Vkorc1 haplotypes with PT, BMD and BMC within each subspecies of Mus. Vkorc1 haplotype sequences divergence between subspecies was associated with PT, BMD and BMC.Phenotypic variation in PT, BMD and BMC within subspecies of Mus, while substantial, appears to be dominated by genetic variation in genes other than the Vkorc1. This was particularly evident for M. m. domesticus, where a single haplotype was observed in conjunction with virtually the entire range of PT, BMD and BMC values of all 5 subspecies of Mus included in this study. Differences in these phenotypes between subspecies also should not be attributed to Vkorc1 variants, but should be viewed as a result of genome wide genetic divergence.The warfarin-sensitive vitamin K epoxide reductase enzyme complex (VKOR) converts vitamin K 2,3-epoxide to vitamin K hydroquinone, a required cofactor for the post-translational gamma-carboxylation of several blood coagulation factors and other vitamin K-dependent proteins, such as osteocalcin (bone Gla protein, BGP) and matrix Gla protein (MGP) [1,2]. MGP has also been found in blood vessel walls and in association with atherosclerotic plaques [3,4]. The vitamin K epoxide reductase complex subunit 1 gene (Vkorc1) appears to be a critical component of the VKOR [5,6].The laboratory mouse is a widely used model organism to study human physiology and medical conditions. Moreover, the Vkorc1 has recently been discussed in the context of gene-drug interactions and disease. For example, genetic polymorphisms in the Vkorc1 could affect anticoagulant therapy with warfarin in humans [7,8]. Genetic variants in the Vkorc1 have been shown associated with genetically determi

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