Vitamin D receptor Fok I polymorphism is associated with low bone mineral density in postmenopausal women: a meta-analysis focused on populations in Asian countries.

OBJECTIVE: To explore the associations between vitamin D receptor (VDR) gene polymorphisms (including Fok I, Bsm I and Apa I) and bone mineral density (BMD) in postmenopausal Asian women. STUDY
DESIGN: Databases of Medline, Embase and Wangfang were retrieved to identify eligible studies, with update to 1st February 2012. Standardized mean difference (SMD) and 95% confidence intervals were calculated by using fixed- or random-effect model. Best genetic comparison model was determined by using the Thakkinstian method.
RESULTS: A total of 14 studies with 3243 healthy postmenopausal Asian women were included in this meta-analysis. Overall, pooled analyses indicated that the f allele of VDR Fok I was significantly associated with decreased BMD in the lumbar spine (ff vs. FF: SMD (95% CI): -0.87 (-1.38, -0.35); P=0.001 for lumbar spine; -0.43 (-0.93, 0.06), P=0.086 for femoral neck). In contrast, we did not observe overall associations between VDR Bsm I and Apa I polymorphisms and BMD in either lumbar spine or femoral neck (Bsm I bb vs. BB: SMD (95% CI): 0.61 (-1.30, 2.53), P=0.531 for lumbar spine; Apa I aa vs. AA: SMD (95% CI): 0.66 (-0.16, 1.48), P=0.113 for lumbar spine). When subgroup analyses were conducted according to countries, Indians carrying the VDR Fok I ff genotype were at risk of low BMD at lumbar spine (ff vs. FF: SMD (95% CI): -0.57 (-0.85, -0.29), P<0.001). Sensitivity analyses indicated that no single study had substantial influence on all combined analyses. In addition, no publication bias was identified.
CONCLUSIONS: This meta-analysis indicated that VDR Fok I, rather than Bsm I and Apa I polymorphisms, is associated with bone mineral density in postmenopausal Asian women (especially for Indian women), and can probably be used with other genetic markers together to identify individuals at high risk of osteoporosis.