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VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey.

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 with decreased BMD among Mexican-American males (n=795; p=0.004). We then tested for associations between VKORC1 SNPs and osteoporosis, but the results did not mirror the associations observed between VKORC1 and BMD, possibly due to small numbers of cases. This is the first report of VKORC1 common genetic variation associated with BMD, and one of the few reports available that investigate the genetics of BMD and osteoporosis in diverse populations.

SUBMITTER: Crawford DC

PROVIDER: S-EPMC3001474 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey.

Crawford Dana C DC Brown-Gentry Kristin K Rieder Mark J MJ

PloS one 20101213 12

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 genera ...[more]

PMID: 21179439

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Project description:BackgroundHypertension is a significant chronic disease that has been linked with bone mineral density (BMD) in various studies. However, the conclusions are contradictory. The purpose of our study was to identify the bone mineral density (BMD) of postmenopausal females and males older than 50 years with hypertension.MethodsThis cross-sectional study of 4,306 participants from the 2005-2010 US National Health and Nutrition Examination Survey explored the relationship between BMD and hypertension. Participants who had a mean systolic blood pressure (SBP) ≥140 mmHg, or a mean diastolic blood pressure (DBP) ≥90 mmHg, or were taking any prescribed medicine for high blood pressure were defined as having hypertension. BMD values were measured at the femoral neck and lumbar vertebrae as the primary outcome. Weight general linear model was used to describe the status of BMD in patients with hypertension. Weighted multivariate regression analysis was conducted to demonstrate the association between hypertension and BMD. Weighted restricted cubic spline (RCS) was used to assess the relationship between BMD and SBP and DBP.ResultsOur study found that there was a positive association between hypertension and lumbar BMD and the lumbar BMD was significantly higher in the presence of hypertension than in the control group in both males (1.072 vs. 1.047 g/cm2) and females (0.967 vs. 0.938 g/cm2; both p < 0.05), but a similar pattern was not found in the femoral neck. Meanwhile, lumbar BMD was positively associated with SBP and negatively associated with DBP both in males and females. The prevalence of low bone mass and osteoporosis at the lumbar vertebrae was lower in male patients with hypertension than in the control group. However, no difference was observed among postmenopausal females between the hypertension and control groups.ConclusionsHypertension was associated with higher BMD at the lumbar vertebrae in both males older than 50 years and postmenopausal females.

Project description:Gallstone disease is one of the most common digestive disorders, affecting more than 30 million Americans. Previous twin studies suggest a heritability of 25% for gallstone formation. To date, one genome-wide association study (GWAS) has been performed in a population of European-descent. Several candidate gene studies have been performed in various populations, but most have been inconclusive. Given that gallstones consist of up to 80% cholesterol, we hypothesized that common genetic variants associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) would also be associated with gallstone risk.To test this hypothesis, the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study as part of the Population Architecture using Genomics and Epidemiology (PAGE) study performed tests of association between 49 GWAS-identified lipid trait SNPs and gallstone disease in non-Hispanic whites (446 cases and 1,962 controls), non-Hispanic blacks (179 cases and 1,540 controls), and Mexican Americans (227 cases and 1,478 controls) ascertained for the population-based Third National Health and Nutrition Examination Survey (NHANES III).At a liberal significance threshold of 0.05, five, four, and four SNP(s) were associated with disease risk in non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. No one SNP was associated with gallstone disease risk in all three racial/ethnic groups. The most significant association was observed for ABCG5 rs6756629 in non-Hispanic whites [odds ratio (OR)?=?1.89; 95% confidence interval (CI)?=?1.44-2.49; p?=?0.0001). ABCG5 rs6756629 is in strong linkage disequilibrium with rs11887534 (D19H), a variant previously associated with gallstone disease risk in populations of European-descent.We replicated a previously associated variant for gallstone disease risk in non-Hispanic whites. Further discovery and fine-mapping efforts in diverse populations are needed to fully describe the genetic architecture of gallstone disease risk in humans.

Dataset Information

VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey.

Publications

VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey.

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