• Lin-Lin Zhang, Xiao-Xiao Wu, Xu-Fan Wang, Dong-Sheng Di, Qian Huang, Rui-Shan Liu, Zong-Wen Shuai, Dong-Qing Ye, and Rui-Xue Leng.
• Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, PR China.
• Ann. Med. 2021 Dec 1; 53 (1): 824-829.

ObjectiveTo investigated the association between single nucleotide polymorphisms (SNPs) in microRNA-146a (miR-146a) gene and susceptibility of rheumatoid arthritis (RA).MethodsWe systemically extracted the genetic data of miR-146a from previous genome-wide association studies (GWASs) of RA. Subsequently, we performed a replication study in an independent Chinese cohort for selected variant. A meta-analysis combined the previous GWASs with the replication study was also conducted. The epigenetic annotation and cytokine assay were used for exploring potential variant function.ResultsThe extracted genetic association data from three previous GWASs showed that the allele T of functional SNP rs2431697 increased RA susceptibility. The significant association for the SNP was also found in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06-1.46, p = 8.69E-03). The estimated effect size for this SNP was larger in Asian population than that in European population (Asian meta-analysis: OR = 1.15, 95% CI = 1.09-1.22, p = 4.37E-07; Tran-ethnic meta-analysis: OR = 1.07, 95% CI = 1.04-1.10, p = 1.79E-06). The cytokine assay also showed that the risk allele T of the SNP rs2431697 is inversely associated with plasma TNF-α levels in health controls (p = .016).ConclusionsIn summary, this study supports that genetic variant in miR-146a gene is associated with RA risk.KEY MESSAGESThe association between SNPs in miR-146a gene and susceptibility of RA was unclear.We investigated the genetic association using GWASs data and a replication study.The SNP rs2431697 in miR-146a gene is associated with RA risk.

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