Yang Ming Ming, Sun Hong Yan, Meng Ting, Qiu Shan Hu, Zeng Qi Qiao, Ng Tsz Kin, Jiang Li, Deng Ting Ming, Zeng Ai Neng, Wang Jun, Luo Xiao Ling
Department of Ophthalmology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University & The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Department of Endocrinology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University & The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Front Immunol. 2021 Feb 11;12:608723. doi: 10.3389/fimmu.2021.608723. eCollection 2021.
Posner-Schlossman syndrome (PSS), also known as glaucomatocyclitic crisis, is an ocular condition characterized by recurrent attacks of anterior uveitis and raised intraocular pressure. Previous studies by our team and others have identified the genetic association of complement pathway genes with uveitis and glaucoma. This study aimed to investigate the complement genes in PSS patients with the view of elucidating the genetic background of the disease. A total of 331 subjects (56 PSS patients and 275 controls) were recruited for this study. We selected 27 variants in six complement pathway genes (, and ) and detected them using TaqMan single nucleotide polymorphism (SNP) Genotyping Assays. Univariate SNP association analysis, haplotype-based association analysis, gene-gene interaction analysis among complement genes, and genotype-phenotype correlation analysis were performed. Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the gene was found to be significantly associated with PSS; there was a significant increase in the frequency of A allele and AA homozygosity in PSS patients than in controls ( = 1.79 × 10; odds ratio (OR) 2.18, 95% CI: 1.44-3.29; = 4.65 × 10; OR 3.66, 95% CI: 1.70-7.85, respectively). The additive effect of -rs800292 and -rs3824988 was identified with an OR of 12.50 (95% CI: 2.16-72.28). Genotype-phenotype analysis indicated that the rs800292 AA genotype was associated with a higher intraocular pressure and higher frequency of recurrence. Unlike a high proportion of human leukocyte antigen (HLA)-B27 positivity in anterior uveitis, only 3 in 56 (5.36%) PSS patients were HLA-B27 positive. In addition, one haplotype block (GC) in the gene showed a nominal association with PSS with an increased risk of 2.04 ( = 0.01; 95% CI: 1.18-3.53), but the -value could not withstand the Bonferroni correction ( > 0.05). This study revealed a genetic association of a variant with PSS as well as its clinical parameters, implying that the alternative complement pathway might play an important role in the pathogenesis of PSS. Further studies to enrich the understanding of the genetic background of PSS and the role of the complement system in ocular inflammation are warranted.
波斯纳-施洛斯曼综合征（PSS），也称为青光眼睫状体炎危象，是一种眼部疾病，其特征为前葡萄膜炎反复发作和眼压升高。我们团队及其他团队之前的研究已确定补体途径基因与葡萄膜炎和青光眼存在遗传关联。本研究旨在调查PSS患者的补体基因，以阐明该疾病的遗传背景。本研究共招募了331名受试者（56名PSS患者和275名对照）。我们在六个补体途径基因（ 、 和 ）中选择了27个变体，并使用TaqMan单核苷酸多态性（SNP）基因分型检测法对其进行检测。进行了单变量SNP关联分析、基于单倍型的关联分析、补体基因间的基因-基因相互作用分析以及基因型-表型相关性分析。在六个补体途径基因的27个变体中，发现 基因上的功能性变体I62V（rs800292）与PSS显著相关；PSS患者中A等位基因频率和AA纯合子频率比对照组显著增加（ = 1.79 × 10；优势比（OR）2.18，95%置信区间：1.44 - 3.29； = 4.65 × 10；OR 3.66，95%置信区间：1.70 - 7.85）。确定了-rs800292和-rs3824988的加性效应，OR为12.50（95%置信区间：2.16 - 72.28）。基因型-表型分析表明，rs800292 AA基因型与更高的眼压和更高的复发频率相关。与前葡萄膜炎中高比例的人类白细胞抗原（HLA）-B27阳性不同，56名PSS患者中只有3名（5.36%）HLA - B27阳性。此外， 基因中的一个单倍型块（GC）与PSS存在名义上的关联，风险增加2.04（ = 0.01；95%置信区间：1.18 - 3.53），但 - 值无法经受Bonferroni校正（ > 0.05）。本研究揭示了一个 变体与PSS及其临床参数的遗传关联，这意味着替代补体途径可能在PSS的发病机制中起重要作用。有必要进行进一步研究，以加深对PSS遗传背景以及补体系统在眼部炎症中作用的理解。
