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  • 标题:Association of Sequence Variations in Vitamin K Epoxide Reductase and γ-Glutamyl Carboxylase Genes with Biochemical Measures of Vitamin K Status
  • 本地全文:下载
  • 作者:Michael D. CROSIER ; Inga PETER ; Sarah L. BOOTH
  • 期刊名称:Journal of Nutritional Science and Vitaminology
  • 印刷版ISSN:0301-4800
  • 电子版ISSN:1881-7742
  • 出版年度:2009
  • 卷号:55
  • 期号:2
  • 页码:112-119
  • DOI:10.3177/jnsv.55.112
  • 出版社:Center for Academic Publications Japan
  • 摘要: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.
  • 关键词:vitamin K epoxide reductase;gamma glutamyl carboxylase;vitamin K;warfarin;polymorphism
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