Genetics of Diabetic Retinopathy in Hispanics

描述（由申请人提供）：糖尿病视网膜病变（DR）是美国20-74岁人群失明的主要原因。 虽然视网膜病变在1型糖尿病中更常见，但大多数新发病例是由于2型糖尿病（T2 DM）。由于美国社会老龄化和少数人群对T2 DM及其微血管并发症的易感性的快速增长，预计DR的社会经济成本将随着T2 DM患病率的增加而增加。然而，严重DR仅发生在约三分之一的患者中，即，一个似乎在遗传上易患这种疾病的亚群。该提案将重点研究西班牙裔DR的遗传学，因为他们有很强的发展T2 DM和DR的倾向。该提案是加州大学洛杉矶分校医学院、Cedars-Sinai医学中心和威斯康星州大学眼部流行病学阅读中心的共同努力。加州大学洛杉矶分校的临床中心将针对225个有3-4个糖尿病同胞的西班牙裔大家庭。我们估计将对1,000对糖尿病同胞进行研究。将通过DR先证者确定家族。糖尿病同胞将进行表型分型，包括收集人口统计学和临床数据以及眼科检查，包括评估视力、测量眼内压和获得标准7视野眼底照片。 眼底照片将在威斯康星州眼部流行病学阅读中心进行阅读和评分。使用顺序全基因组测试，我们将在每批基因分型（96个样本）完成时进行10 cM全基因组搜索，以确定候选区域。将利用非参数同胞对连锁分析和方差分量连锁分析来识别可能含有导致DR的基因的区域。对于具有连锁证据的8个最佳区域，将对8个新标记进行基因分型以缩小候选区域。该项目的成功完成将导致在初始阶段定位新的基因（S）赋予DR的易感性。表征这些基因的产物将提高我们对DR的发病机制的理解，并导致新的预防和治疗策略的发展。此外，DR遗传标记的可用性将允许早期识别处于风险中的患者，这些患者应该是强化血糖和血压控制的目标。

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR) is the leading cause of blindness in people aged 20-74 years in the United States. Although retinopathy is more common in type 1 diabetes, the majority of new cases are due to type 2 diabetes (T2DM). The socioeconomic cost of DR is expected to escalate with the increasing prevalence of T2DM due to the aging of the American society and the rapid growth of minority populations with predilection to T2DM and its microvascular complications. Severe DR occurs only, however, in approximately one-third of patients, i.e., a subgroup that appears to be genetically predisposed to the disease. This proposal will focus on studying genetics of DR in Hispanics because they have a strong propensity for development of T2DM and DR. This proposal is a joint effort among the UCLA School of Medicine, Cedars-Sinai Medical Center, and the University of Wisconsin Ocular Epidemiology Reading Center. The clinical center at UCLA will target 225 large Hispanic families with 3-4 diabetic sibs. We estimate that 1,000 diabetic sib-pairs will be studied. The families will be ascertained through a proband with DR. Diabetic sibs will undergo phenotyping which will include collection of demographic and clinical data and an eye examination that will include assessment of visual acuity, measurement of intraocular pressure, and obtaining standard 7-field fundus photographs. Fundus photographs will be read and graded at the Wisconsin Ocular Epidemiology Reading Center. Using the sequential genome-wide test, we will perform a 10 cM genome-wide search when each batch of genotyping (96 samples) is completed to identify candidate regions. Non-parametric sib-pair linkage analysis and variance components linkage analysis will be utilized to identify regions that may contain genes contributing to DR. For the eight best regions identified with evidence for linkage, eight new markers will be genotyped to narrow the candidate region. Successful completion of this project will result in the initial phase in locating novel gene(s) that confer susceptibility to DR. Characterization of the products of these genes will enhance our understanding of the pathogenesis of DR and lead to development of new preventive and therapeutic strategies. Moreover, availability of genetic markers for DR will allow early identification of patients at risk who should be targeted for intensive glycemic and blood pressure control.