vkorc1 common variation and bone mineral density in the third national health and nutrition examination surveyvkorc1常见变异和骨矿物质密度在第三次全国健康和营养调查.pdfVIP

VKORC1 Common Variation and Bone Mineral Density in the Third National Health and Nutrition Examination Survey 1,2 1 3 Dana C. Crawford *, Kristin Brown-Gentry , Mark J. Rieder 1 Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America, 2 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America, 3 Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America Abstract Osteoporosis, defined by low bone mineral density (BMD), is common among postmenopausal women. The distribution of BMD varies across populations and is shaped by both environmental and genetic factors. Because the candidate gene vitamin K epoxide reductase complex subunit 1 (VKORC1) generates vitamin K quinone, a cofactor for the gamma- carboxylation of bone-related proteins such as osteocalcin, we hypothesized that VKORC1 genetic variants may be associated with BMD and osteoporosis in the general population. To test this hypothesis, we genotyped six VKORC1 SNPs in 7,159 individuals from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a nationally representative sample linked to health and lifestyle variables including BMD, which was measured using dual energy x-ray absorptiometry (DEXA) on four regions of the proximal femur. In adjusted models stratified by race/ethnicity and sex, SNPs rs9923231 and rs9934438 were associated with increased BMD (p = 0.039 and 0.024, respectively) while rs8050894 was associated with decreased BMD (p = 0.016) among non-Hispanic black males (n = 619). VKORC1 rs2884737 was associated wi