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型糖尿病中更为常见，但大多数新病例是由2型糖尿病（T2DM）引起的。由于美国社会的老龄化以及易患2型糖尿病及其微血管并发症的少数群体的快速增长，DR的社会经济成本预计会随着2型糖尿病患病率的增加而上升。然而，严重的DR只发生在大约三分之一的患者中，即一个似乎在遗传上易患该疾病的亚组。该提案将重点研究西班牙裔糖尿病和DR的遗传学，因为他们有很强的2型糖尿病和DR的发展倾向。该提案是加州大学洛杉矶分校医学院、雪松-西奈医学中心和威斯康星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个糖尿病兄弟姐妹的拉美裔大家庭。我们估计将研究1000对糖尿病兄弟姐妹。糖尿病兄弟姐妹将进行表型分析，包括收集人口统计学和临床数据，并进行眼科检查，包括评估视力、测量眼压和获得标准的7场眼底照片。眼底照片将在威斯康星眼流行病学阅读中心阅读并评分。使用序列全基因组检测，我们将在每批基因分型（96个样本）完成后进行10 cM全基因组搜索，以确定候选区域。非参数同胞对连锁分析和方差成分连锁分析将被用于识别可能包含导致dr的基因的区域。对于鉴定出的具有连锁证据的8个最佳区域，将对8个新的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定位具有DR易感性的新基因的初始阶段，这些基因产物的表征将增强我们对DR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有风险的患者，他们应该成为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.