Association Between the FokI and ApaI Polymorphisms in the Vitamin D Receptor Gene and Intervertebral Disc Degeneration: A Systematic Review and Meta-Analysis

Background: Evidence supporting an association of intervertebral disc degeneration (DD) with polymorphisms of the vitamin D receptor (VDR) gene has been controversial. We performed a meta-analysis of these studies to determine if there was substantial evidence to support such an association between the VDR polymorphisms and DD. Methods: PubMed, Embase, and Science Direct databases were searched for studies that investigated associations of the FokI (rs2228570, rs10735810), and ApaI (rs7975253) polymorphisms of the VDR gene with DD. From the extracted genotype data from 14 publications, we estimated risk (odds ratio [OR] with 95% confidence intervals). Results: Overall associations of FokI with DD were absent (OR 0.96-1.04, p = 0.73-0.95) with heterogeneity in the dominant and codominant models (p(heteroegeneity) <0.10, I-2 = 47-57%). Post-outlier pooled effects yielded dominant significance indicating reduced risk (OR 0.77, p = 0.01) with concomitant zero heterogeneity (I-2 = 0%). ApaI effects pointed to reduced risks, with overall dominant significance (OR 0.69, p = 0.04) and Asian subgroup nonsignificance (OR 0.75-0.93, p = 0.17-0.74). In FokI, Non-Hispanic Caucasians (OR 0.77, p = 0.01) and males (OR 0.36-0.66, p = 0.001-0.04) were protected but not Hispanic Caucasians (OR 1.39-1.85, p = 0.006-0.05) and females (OR 1.72, p = 0.05). Tests of interaction between the genders highlighted female susceptibility and male protection (p = 0.001-0.005). Zero heterogeneity (I-2 = 0%) is a key strength of these significant effects. Conclusion: This meta-analysis confirmed the protective role of the ApaI polymorphism, however, susceptibility and protective effects of the FokI polymorphism may be ethnic and gender specific.