PTPN22 gene polymorphism and susceptibility to rheumatoid arthritis (RA): Updated systematic review and meta-analysis

Several genome-wide association studies have revealed a genetic background with respect to susceptibility to rheumatoid arthritis (RA). Although several individual case-control studies have evaluated the role of protein tyrosine phosphatase non-receptor 22 (PTPN22) gene rs2476601 single nucleotide polymorphism (SNP) in conferring a risk for RA, the results have been conflicting. Hence, this meta-analysis was aimed to provide a solution for this issue.

To search for studies assessing the association between the PTPN22 gene rs2476601 SNP and the risk of RA, a systematic search was conducted in the main databases, including PubMed, Scopus and Web of Science, prior to December 2019. The odds ratio (OR) and corresponding 95% confidence interval (CI) was calculated to assess the possibility of association risk.

The literature search identified 52 case-control studies. The pooled analysis detected significant positive association of rs2476601 in all genetic models, including dominant model (OR = 1.69, 95% CI = 1.55-1.84, P < 0.001), recessive model (OR = 2.50, 95% CI = 2.06-3.05, P < 0.001), allelic model (OR = 1.80, 95% CI = 1.60-2.2, P < 0.001), TT versus CC model (OR = 2.79, 95% CI = 2.28-3.41, P < 0.001) and CT versus CC model (OR = 1.59, 95% CI = 1.50-1.67, P < 0.001). Analyses based on population stratification indicated that rs2476601 SNP strongly increased the risk of RA in Caucasians and Africans under all genotype models.

This meta-analysis reports that the PTPN22 gene rs2476601 SNP increases RA risk, especially in Caucasians and Africans.