4.3 Article

Meta-Analysis of the Genetic Association between PTPN22 and CTLA-4 Variants and Risk of Uveitis

Journal

OPHTHALMIC RESEARCH
Volume 65, Issue 3, Pages 264-275

Publisher

KARGER
DOI: 10.1159/000521301

Keywords

Uveitis; PTPN22; CTLA-4; Polymorphism; Meta-analysis

Categories

Funding

  1. National Natural Science Foundation Project [81770916, 81400389]
  2. Chongqing Science & Technology Foundation Project [cstc2014jcyjA10111]

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This study conducted a meta-analysis to explore the association between genetic variants of PTPN22 and CTLA-4 with uveitis susceptibility. The results showed that PTPN22 rs2488457 was associated with increased susceptibility to uveitis, especially in the Asian region. CTLA-4 rs231775 was found to confer protection against uveitis in African populations, while CTLA-4 rs4553808 was associated with an increased risk of Behcet's disease.
Background: Though the risk of protein tyrosine phosphatase nonreceptor 22 (PTPN22) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genetic variants with uveitis have been developed, the combined results still remain uncertain and controversial. Objectives: The aim of this study was to perform a meta-analysis to estimate the precise association of PTPN22 (rs2488457 and rs2476601) and CTLA-4 (rs231775, rs5742909, rs4553808, and rs3087243) polymorphisms with uveitis susceptibility. Method: 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. Results: Our meta-results indicated that PTPN22 rs2488457 conferred positive susceptibility to uveitis (odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.02-1.38, p = 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, p = 0.046). For CTLA-4 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, p < 0.001). For CTLA-4 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, p = 0.042). Conclusions: Our research revealed that PTPN22 rs2488457 conferred strong susceptibility to uveitis in general, especially in the Asian region. CTLA-4 rs231775 conveyed protection against uveitis in African populations, and CTLA-4 rs4553808 displayed an increased risk of BD. (C) 2022 The Author(s).Published by S. Karger AG, Basel

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