Association Between Interleukin-6 Gene Polymorphisms And Bone Mineral Density: A Meta-Analysis

Background: Many studies have examined the association between interleukin-6 (IL-6) gene polymorphisms and bone mineral density (BMD). However, the results remain conflicting. To assess the relationship more precisely, a meta-analysis was performed. Methods: The PubMed, Embase, Chinese BioMedical Literature (CBM), Wanfang, and China National Knowledge Infrastructure (CNKI) database were searched for relevant articles published up to March 2013. Weighted mean difference (WMD) and 95% confidence interval (95% CI) were calculated using a fixed-effects or random-effects model. Results: A total of 16 articles with 11,957 subjects were investigated in this meta-analysis. Overall, -634C/G polymorphism was significantly associated with BMD at the femoral neck (WMD, -0.016g/cm(2); 95% CI, -0.028 to -0.003g/cm(2)), lumbar spine (WMD, -0.049g/cm(2); 95% CI, -0.069 to -0.030g/cm(2)), and whole body (WMD, -0.023g/cm(2); 95% CI, -0.037 to -0.009g/cm(2)) for GG versus CC+CG. In subgroup analyses stratified by ethnicity, individuals carrying -634GG genotype had a significantly lower mean BMD at any skeletal site examined, compared with individuals with -634CC or -634CG genotype in Asian populations. For -174G/C polymorphism, the BMD differences between CC+CG and GG genotype were 0.004g/cm(2) at the distal radius (95% CI, 0.004 to 0.005g/cm(2)), 0.011g/cm(2) at the trochanter (95% CI, 0.002 to 0.020g/cm(2)), and 0.017g/cm(2) at the Ward's triangle (95% CI, 0.003 to 0.032g/cm(2)). No significant publication bias was observed in either the -634C/G or -174G/C polymorphism. Conclusions: This suggests that there are modest effects of the -634C/G and -174G/C polymorphisms on BMD. Large-scale and well-designed studies are required to further investigate gene-gene and gene-environment interactions on IL-6 polymorphisms and BMD in various populations.