Abstract
γ-Glutamyl carboxylation, a reaction essential for the activity of vitamin K—dependent proteins, requires the concerted actions of γ-glutamyl carboxylase (GGCX), vitamin K 2,3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and genotyped 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G<A (130.8% ± 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% ± 0.7%, n = 728) or the AA (125.4% ± 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G<A change leads to the substitution of Gln for Arg at amino acid residue 325 (Arg325Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G<A and CALU 20943T<A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K—dependent γ-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.
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Kimura, R., Kokubo, Y., Miyashita, K. et al. Polymorphisms in Vitamin K—Dependent γ-Carboxylation—Related Genes Influence Interindividual Variability in Plasma Protein C and Protein s Activities in the General Population. Int J Hematol 84, 387–397 (2006). https://doi.org/10.1532/IJH97.06082
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DOI: https://doi.org/10.1532/IJH97.06082