CFH I62V as a Putative Genetic Marker for Posner-Schlossman Syndrome.
CFH I62V as a Putative Genetic Marker for Posner-Schlossman Syndrome.
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DOI：
10.3389/fimmu.2021.608723
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发表时间：
2021
影响因子：
7.3
通讯作者：
Luo XL
中科院分区：
文献类型：
--
作者：
Yang MM;Sun HY;Meng T;Qiu SH;Zeng QQ;Ng TK;Jiang L;Deng TM;Zeng AN;Wang J;Luo XL
目的：波斯纳-施洛斯曼综合征（PSS），也称为青光眼睫状体危象，是一种以前葡萄膜炎反复发作和眼压升高为特征的眼部疾病。我们团队和其他人之前的研究已经确定了补体途径基因与葡萄膜炎和青光眼的遗传关联。本研究旨在研究PSS患者的补体基因，以期阐明该疾病的遗传背景。方法：本研究共招募了 331 名受试者（56 名 PSS 患者和 275 名对照者）。我们选择了 6 个补体途径基因（SERPING1、C2、CFB、CFH、C3 和 C5）中的 27 个变体，并使用 TaqMan 单核苷酸多态性 (SNP) 基因分型测定法检测它们。进行单变量SNP关联分析、基于单倍型的关联分析、补体基因之间的基因-基因相互作用分析以及基因型-表型相关分析。结果：在6个补体途径基因的27个变异体中，CFH基因的功能变异体I62V（rs800292）被发现与PSS显着相关； PSS 患者中 A 等位基因和 AA 纯合性的频率显着增加（分别为 P = 1.79 × 10−4；比值比 (OR) 2.18，95% CI：1.44–3.29；P = 4.65 × 10−4；OR 3.66，95% CI：1.70–7.85）。 CFH-rs800292 和 SERPING1-rs3824988 的相加效应被确定为 OR 为 12.50 (95% CI: 2.16–72.28)。基因型-表型分析表明rs800292 AA基因型与较高的眼压和较高的复发频率相关。与前葡萄膜炎中人类白细胞抗原 (HLA)-B27 阳性的比例较高不同，56 名 PSS 患者中只有 3 名 (5.36%) 呈 HLA-B27 阳性。此外，SERPING1 基因中的一个单倍型块 (GC) 显示与 PSS 名义相关，风险增加为 2.04（P = 0.01；95% CI：1.18–3.53），但 P 值无法经受 Bonferroni 校正（Pcorr > 0.05）。结论：本研究揭示了 CFH 变异与 PSS 及其临床参数的遗传关联，这意味着补体旁路途径可能在 PSS 的发病机制中发挥重要作用。需要进一步研究以丰富对 PSS 遗传背景和补体系统在眼部炎症中的作用的理解。
Objective: 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. Methods: 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 (SERPING1, C2, CFB, CFH, C3, and C5) 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. Results: Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the CFH 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 (P = 1.79 × 10−4; odds ratio (OR) 2.18, 95% CI: 1.44–3.29; P = 4.65 × 10−4; OR 3.66, 95% CI: 1.70–7.85, respectively). The additive effect of CFH-rs800292 and SERPING1-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 SERPING1 gene showed a nominal association with PSS with an increased risk of 2.04 (P = 0.01; 95% CI: 1.18–3.53), but the P-value could not withstand the Bonferroni correction (Pcorr > 0.05). Conclusion: This study revealed a genetic association of a CFH 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.
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DOI：
10.1016/s0140-6736(08)61348-3
发表时间：
2008-11-22
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ennis S;Jomary C;Mullins R;Cree A;Chen X;Macleod A;Jones S;Collins A;Stone E;Lotery A
通讯作者：
Lotery A
影响因子：
1.2
作者：
Lippert, Jason;Falgiani, Michael;Ganti, Latha
通讯作者：
Ganti, Latha
DOI：
10.1073/pnas.83.10.3161
发表时间：
1986-05-01
影响因子：
11.1
作者：
DAVIS, AE;WHITEHEAD, AS;ROSEN, FS
通讯作者：
ROSEN, FS
CFH和CFB基因多态性与2型糖尿病患者的视网膜病变的关联。
影响因子：
4.6
作者：
Wang J;Yang MM;Li YB;Liu GD;Teng Y;Liu XM
通讯作者：
Liu XM
影响因子：
3.9
作者：
Aigner, Christof;Gaggl, Martina;Sunder-Plassmann, Gere
通讯作者：
Sunder-Plassmann, Gere