Genetic analysis of the relationship between bone mineral density and low-density lipoprotein receptor-related...

A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.

Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.

A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02 g/cm², 95% CI = 0.01-0.03, P < 10⁻⁴; at femur neck (FN): WMD = 0.01 g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02 g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02 g/cm², 95% CI = 0.02-0.03, P < 10⁻⁵; WMD at FN = 0.01 g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03 g/cm², 95% CI = 0.01-0.05, P = 0.005).

This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.