Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts
Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts
复制标题
DOI：
10.1167/iovs.06-0991
复制
发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Kinoshita, Shigeru
中科院分区：
文献类型：
--
作者：
Matsuda, Akira;Ebihara, Nobuyuki;Kinoshita, Shigeru
目的.先前的报告显示遗传易感性特应性皮炎（AD）。AD的一些严重并发症表现在眼睛中，如白内障、视网膜脱离和角膜结膜炎。本研究旨在探讨特应性痴呆相关基因与眼部并发症（眼AD）患者之间的遗传关联。780例眼AD患者和282例健康对照受试者参加了特应性相关基因（FCERB，IL 13和IFNGR 1）与眼AD之间的关联研究。进行单核苷酸多态性（SNPs）的遗传关联研究和功能分析。IFNGR 1启动子区的-56TT基因型与隐性模型下眼AD风险增加显著相关（卡方检验，原始P = 0.0004，优势比2.57）。-56TT基因型在特应性白内障中更常见。报告基因测定显示，在用IFN-γ刺激后，含有-56 T等位基因（眼AD患者中的常见等位基因）的IFNGR 1基因启动子构建体在透镜上皮细胞（LEC）中表现出比含有-56 C等位基因的构建体更高的转录活性。实时荧光定量PCR分析表明，IFNGR 1 mRNA在特应性白内障晶状体上皮细胞中的表达高于老年性白内障。IFN-γ和LPS刺激后，过表达IFNGR 1的LEC的iNOS表达增强。IFNGR 1启动子中的-56T等位基因导致更高的IFNGR 1转录活性，并代表特应性白内障的遗传风险因素。
PURPOSE. Previous reports have shown genetic predisposition for atopic dermatitis ( AD). Some of the severe complications of AD manifest in the eye, such as cataract, retinal detachment, and keratoconjunctivitis. This study was conducted to examine the genetic association between the atopy-related genes and patients with ocular complications ( ocular AD).METHODS. Seventy-eighty patients with ocular AD and 282 healthy control subjects were enrolled in an investigation of the association between the atopy-related genes ( FCERB, IL13, and IFNGR1) and ocular AD. Genetic association studies and functional analysis of single nucleotide polymorphisms ( SNPs) were performed.RESULTS. The -56TT genotype in the IFNGR1 promoter region was significantly associated with an increased risk of ocular AD under recessive models ( chi(2) test, raw P = 0.0004, odds ratio 2.57). The -56TT genotype was more common in atopic cataracts. A reporter gene assay showed that, after stimulation with IFN-gamma, the IFNGR1 gene promoter construct that contained the -56T allele, a common allele in ocular AD patients, manifested higher transcriptional activity in lens epithelial cells ( LECs) than did the construct with the -56C allele. Real-time PCR analysis demonstrated higher IFNGR1 mRNA expression in the LECs in atopic than in senile cataracts. iNOS expression by IFNGR1-overexpressing LECs was enhanced on stimulation with IFN-gamma and LPS.CONCLUSIONS. The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts.