Lack of Associations between Endoplasmic Reticulum Aminopeptidase 2 Gene Polymorphisms and Ankylosing Spondylitis: A Meta-analysis with Trial Sequential Analysis

Background: Endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is reported to be associated with inflammation-related diseases. Several studies have investigated the associations of ERAP2 gene polymorphisms and susceptibility to ankylosing spondylitis (AS). However, the findings of those studies were inconsistent. The aim of this study was to elucidate the associations by a meta-analysis with trial sequential analysis (TSA). Methods: Online databases of PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, and CNKI were searched to identify eligible studies on the associations of ERAP2 gene polymorphisms and AS. Study quality was judged based on the Newcastle-Ottawa scale (NOS). Strengths of associations were presented by P-value, odds ratios (ORs), and 95% confidence intervals (95%CIs). TSA was employed to evaluate the information size and statistical power. Results: A total of six studies encompassing 2774 AS patients and 4119 disease-free controls were eligible for this meta-analysis. Five studies reported rs2248374 polymorphism and three studies reported rs2549782 polymorphism. The pooled data suggested that the two polymorphisms were not significantly associated with AS susceptibility: rs2248374, A vs. G, OR = 0.94, 95%CI 0.86-1.02, P = .14; rs2549782, T vs. G, OR = 1.03, 95%CI 0.95-1.12, P = .45. TSA indicated that the sample sizes appeared to be inadequate to obtain a positive outcome. Conclusion: The present findings of this study do not support any evidence on the associations of rs2248374 and rs2549782 polymorphisms in the ERAP2 gene and susceptibility to AS. Additional well-designed and large-sample studies in diverse ethnicities are encouraged to validate the current findings.

Automated summary

The meta-analysis found no significant association between ERAP2 gene polymorphisms rs2248374 and rs2549782 and susceptibility to AS. Trial sequential analysis indicated that the sample sizes may have been inadequate to establish a positive outcome. Additional well-designed studies in diverse ethnicities are recommended to validate the current findings.