Meta-Analysis of the Genetic Association between <b><i>PTPN22</i></b> and <b><i>CTLA-4</i></b> Variants and Risk of Uveitis

Abstract

<b><i>Background:</i></b> Though the risk of protein tyrosine phosphatase nonreceptor 22 (<i>PTPN22</i>) and cytotoxic T-lymphocyte antigen-4 (<i>CTLA-4</i>) genetic variants with uveitis have been developed, the combined results still remain uncertain and controversial. <b><i>Objectives:</i></b> The aim of this study was to perform a meta-analysis to estimate the precise association of <i>PTPN22</i> (rs2488457 and rs2476601) and <i>CTLA-4</i> (rs231775, rs5742909, rs4553808, and rs3087243) polymorphisms with uveitis susceptibility. <b><i>Method:</i></b> Five electronic databases (PubMed, Embase, Web of Science, China Biomedical Database, and China National Knowledge Infrastructure) were systematically searched for relevant literature up to July 20, 2021. All statistical analyses were evaluated by Stata 12.0 software and R programming language. <b><i>Results:</i></b> Our meta-results indicated that <i>PTPN22</i> rs2488457 conferred positive susceptibility to uveitis (odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.02–1.38, <i>p</i> = 0.029). In stratified analysis by ethnicity, the rs2488457 C allele had a growing tendency toward uveitis in the Asian region (OR = 1.21, 95% CI = 1.00–1.45, <i>p</i> = 0.046). For <i>CTLA-4</i> rs231775, subgroup analysis based on ethnicity manifested a negative association among uveitis individuals in the Africa region (OR = 0.25, 95% CI = 0.19–0.33, <i>p</i> &#x3c; 0.001). For <i>CTLA-4</i> rs4553808, subgroup analysis by the disease type revealed that the GG genotype was associated with an elevated risk of Behcet’s disease (BD) (OR = 3.22, 95% CI = 1.05–9.90, <i>p</i> = 0.042). <b><i>Conclusions:</i></b> Our research revealed that <i>PTPN22</i> rs2488457 conferred strong susceptibility to uveitis in general, especially in the Asian region. <i>CTLA-4</i> rs231775 conveyed protection against uveitis in African populations, and <i>CTLA-4</i> rs4553808 displayed an increased risk of BD.