Genetics of Diabetic Retinopathy in Hispanics

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型糖尿病引起的。 (T2 DM)。随着T2 DM患病率的增加，DR的社会经济成本预计将上升 对美国社会老龄化和易患T2 DM的少数民族人口的快速增长 及其微血管并发症。然而，只有大约三分之一的患者会发生严重的DR， 即似乎在遗传上易患这种疾病的亚群。这份提案将重点研究 西班牙裔人DR的遗传学，因为他们有很强的T2 DM和DR的发病倾向 该提案是加州大学洛杉矶分校医学院、锡达斯-西奈医学中心和 威斯康星大学眼科流行病学阅读中心。加州大学洛杉矶分校的临床中心将瞄准225人 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。这个 有糖尿病兄弟姐妹的先证者家庭将接受表型鉴定，这将 包括收集人口统计和临床数据以及将包括评估 视力，测量眼压，并获得标准的7视野眼底照片。 眼底照片将在威斯康星州眼科流行病学阅读中心阅读并分级。vbl.使用 连续的全基因组测试，我们将执行10 cM的全基因组搜索，当每批 完成了(96个样本)的基因分型，以确定候选区域。非参数同胞对连锁分析 将利用方差分量连锁分析来识别可能包含基因的区域 对Dr的贡献为八个最好的区域确定了链接的证据，八个新的标记将是 对候选区域进行基因分型以缩小范围。该项目的成功完成将导致初步阶段 在定位对DR易感的新基因(S)时，表征这些基因的产物将 加强对DR发病机制的认识，促进新的预防和治疗方法的发展 治疗策略。此外，DR遗传标记的可获得性将使早期识别 应重点控制血糖和血压的高危患者。

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.