Vitamin D Receptor Gene and Aggrecan Gene Polymorphisms and the Risk of Intervertebral Disc Degeneration — A Meta-Analysis

BACKGROUND A series of studies have been conducted to evaluate the associations between vitamin D receptor (VDR) and aggrecan variable numbers of tandem repeat (VNTR) polymorphisms and the risk of intervertebral disc degeneration (IDD), but produced conflicting results. OBJECTIVE we performed a meta-analysis to address a more accurate estimation of the associations between the above gene polymorphisms and the risk of IDD. METHODS A comprehensive literature search was conducted to identify all the relevant studies. The fixed or random effect model was selected based on the heterogeneity test among studies evaluated using the I(2). Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS A total of 9, 5, 3, and 7 studies were finally included in the analyses for the associations between the VDR TaqI (rs731236), FokI (rs2228570), ApaI (rs7975232), or aggrecan VNTR polymorphisms and the risk of IDD, respectively. The combined results showed that none of the VDR (TaqI, FokI, ApaI) polymorphisms were significantly associated with the risk of IDD. In contrast, the alleles with shorter VNTR length was found to significantly increase the risk of IDD (≦25 vs. >25: OR = 1.850, 95%CI 1.477-2.318; ≦23 vs. >23: OR = 1.955, 95%CI 1.41-2.703). Subgroup analysis confirmed the above results. After excluding studies deviated from Hardy-Weinberg equilibrium (HWE) in controls, no other studies were found to significantly influence the pooled effects in each genetic model. No potential publication bias was detected. CONCLUSION This meta-analysis suggested that the alleles with shorter VNTR length significantly increased the risk of IDD, while the VDR (TaqI, FokI, ApaI) gene polymorphisms were not significantly associated with the risk of IDD. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.