Genetic polymorphism of the estrogen receptor alpha gene and susceptibility to osteoarthritis: evidence based on 15,022 subjects

Several lines of evidence suggest that estrogen receptor alpha (ER-α) gene polymorphism may influence the development of osteoarthritis (OA). However, the results are inconsistent. The aim of this study was to explore using a meta-analysis whether rs2234693 (ER-α PvuII T/C) polymorphism confers significant susceptibility to OA.A systematic search of all relevant studies published through 17 August 2014 was conducted using the PubMed, Web of Science, Embase, Cochrane database, Current Controlled Trials, Clinicaltrials.gov, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar. All statistical analyses were done with Review Manager 5.1.4. Twelve articles involving 15 studies were included in the final meta-analysis, which contained 6417 OA cases and 8605 controls. Overall, no significant association was found between the rs2234693 polymorphism and OA risk when all studies were pooled into the meta-analysis (for C allele vs. T allele: OR = 0.99, 95% CI = 0.94-1.04, p = 0.63; for C/C vs. T/T: OR = 0.97, 95% CI = 0.87-1.08, p = 0.53; for C/C vs. T/C + T/T: OR = 0.96, 95% CI = 0.88-1.06, p = 0.43; for C/C + T/C vs. T/T: OR = 1.00, 95% CI = 0.89-1.14, p = 0.94). In the subgroup analysis, significant association was found between the rs2234693 polymorphism and the OA risk in the knee osteoarthritis (KOA) group (for C/C + T/C vs. T/T: OR = 1.15, 95% CI = 1.02-1.29, p = 0.02).The present meta-analysis suggests that the rs2234693 polymorphism is associated with an increased KOA risk. Additional well designed genome-wide association studies are required to confirm the result.