A Meta-analysis Assessing the Association Between COL11A1 and GDF5 Genetic Variants and Intervertebral Disc Degeneration Susceptibility.

STUDY DESIGN:Meta-analysis to collect relevant studies to assess the association between COL11A1 and GDF5 genetic variants and susceptibility to IDD. OBJECTIVE:The aim of this study was to assess whether or not COL11A1 and GDF5 genetic variants were associated with susceptibility to IDD. SUMMARY OF BACKGROUND DATA:IDD or LDH is a major public health problem. There have been several studies evaluating the relationship between COL11A1 and GDF5 genetic variants with risk of intervertebral disc degeneration (IDD). However, the studies were limited in discrete outcome and sample size, and some of the results were contradictory. METHODS:We systematically searched the relevant publications in electronic databases. Eligible studies were included based on the defined criteria. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were received using 15. Subgroup analysis, sensitivity analysis, publication bias, and the "Trim and fill" method were performed in the meta-analysis. RESULTS:A total of 3287 IDD cases and 5115 controls were incorporated into the meta-analysis. Our results demonstrated that COL11A1 rs1676486 was significantly associated with increased IDD susceptibility under all genetic models (allele model T vs. C: OR = 1.40, 95% CI 1.23-1.59, P = 0.000; homozygote model TT vs. CC: OR = 1.89, 95%CI 1.40-2.56, P = 0.000; dominant model TT+TC vs. CC: OR = 1.52, 95% CI 1.29-1.80, P = 0.000; recessive model TT vs. TC + CC: OR = 1.58, 95% CI 1.18-2.12, P = 0.002). However, GDF5 rs143383 was not (allele model T vs. C: OR = 1.15, 95% CI 0.91-1.44, P = 0.244; homozygote model TT vs. CC: OR = 1.22, 95% CI 0.75-2.00, P = 0.429; dominant model TT vs. CC+CT: OR = 1.22, 95% CI 0.95-1.57, P = 0.112; recessive model TC + TT vs. CC: OR = 1.12, 95% CI 0.73-1.73, P = 0.594). Subgroup analysis indicated ethnicity was not the source of heterogeneity. Sensitivity analysis, publication bias, and the "Trim and fill" method demonstrated the meta-analysis was of reliability. CONCLUSION:Our results suggested that COL11A1 rs1676486 was significantly associated with IDD and the T allele was a risky factor. However, GDF5 rs143383 was not. LEVEL OF EVIDENCE:1.

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