Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China.
Medicine (Baltimore). 2024 Nov 29;103(48):e40663. doi: 10.1097/MD.0000000000040663.
The genetic basis of iridocyclitis, an inflammatory eye disease, remains poorly understood, particularly in relation to autoimmune diseases. This study aimed to explore the causal associations between 6 immune-related diseases and iridocyclitis using Mendelian randomization (MR). A total of 230 single nucleotide polymorphisms (SNPs) significantly associated with systemic lupus erythematosus, ankylosing spondylitis (AS), rheumatoid arthritis (RA), Graves disease (GD), Crohn disease (CD), and allergic contact dermatitis were identified based on stringent MR assumptions. These SNPs served as instrumental variables to estimate the causal effect of each autoimmune disease on iridocyclitis risk. The analysis utilized the inverse variance weighted method, complemented by sensitivity analyses including MR-Egger regression and leave-one-out testing to assess pleiotropy and robustness. The MR analysis revealed significant associations between genetically predicted AS (odds ratio [OR]: 1.544, 95% confidence interval [CI]: 1.494-1.595, P = 1.99 × 10-226), RA (OR: 1.207, 95% CI: 1.052-1.385, P = .003), and CD (OR: 1.654, 95% CI: 1.263-2.166, P = 2.54 × 10⁻⁶) with an increased risk of iridocyclitis. Conversely, higher genetically predicted GD was associated with a decreased risk of iridocyclitis (OR: 0.763, 95% CI: 0.674-0.865, P = .0002). Although systemic lupus erythematosus and allergic contact dermatitis appeared to have a protective effect, these results were not statistically significant, and no causal relationship could be established. Heterogeneity was observed among the SNPs, but no significant horizontal pleiotropy was detected. This study identifies potential genetic links between AS, RA, CD, GD, and the risk of iridocyclitis, providing new insights into the genetic underpinnings of this eye disease. The results support the need for further investigation into the genetic and molecular mechanisms underlying these associations.
免疫性眼病——虹膜睫状体炎的遗传基础仍知之甚少，尤其是与自身免疫性疾病相关的部分。本研究旨在采用孟德尔随机化（MR）方法探索 6 种免疫相关疾病与虹膜睫状体炎之间的因果关联。基于严格的 MR 假设，共鉴定出 230 个与系统性红斑狼疮、强直性脊柱炎（AS）、类风湿关节炎（RA）、格雷夫斯病（GD）、克罗恩病（CD）和过敏性接触性皮炎显著相关的单核苷酸多态性（SNP）。这些 SNP 作为工具变量，用于估计每种自身免疫性疾病对虹膜睫状体炎风险的因果效应。分析采用逆方差加权法，补充 MR-Egger 回归和逐一剔除检验进行敏感性分析，以评估偏倚和稳健性。MR 分析显示，遗传预测的 AS（比值比 [OR]：1.544，95%置信区间 [CI]：1.494-1.595，P = 1.99×10-226）、RA（OR：1.207，95%CI：1.052-1.385，P =.003）和 CD（OR：1.654，95%CI：1.263-2.166，P = 2.54×10-6）与虹膜睫状体炎风险增加显著相关。相反，遗传预测的 GD 较高与虹膜睫状体炎风险降低相关（OR：0.763，95%CI：0.674-0.865，P =.0002）。尽管系统性红斑狼疮和过敏性接触性皮炎似乎具有保护作用，但这些结果无统计学意义，无法确定因果关系。SNP 间存在异质性，但未检测到明显的水平性偏倚。本研究鉴定出 AS、RA、CD、GD 与虹膜睫状体炎风险之间的潜在遗传联系，为该眼病的遗传基础提供了新的见解。研究结果支持进一步研究这些关联的遗传和分子机制的必要性。
