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型糖尿病中更常见，但大多数新发病例是由于2型糖尿病 （T2DM）。随着T2 DM患病率的增加，DR的社会经济成本预计会上升， 美国社会的老龄化和T2 DM易感少数群体的快速增长 及其微血管并发症。然而，严重的DR仅发生在约三分之一的患者中， 也就是说，一个似乎在遗传上易患这种疾病的亚群。这项建议将着重研究 西班牙裔人的DR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，雪松西奈医学中心和 威斯康星州大学眼部流行病学阅读中心。加州大学洛杉矶分校的临床中心将目标225 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。的 家庭将通过先证者与DR确定。糖尿病同胞将进行表型， 包括收集人口统计和临床数据以及进行眼科检查， 视力、眼内压测量和获得标准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 在全基因组序列检测中，我们将在每批基因组中进行10 cM的全基因组搜索， 完成基因分型（96个样品）以鉴定候选区域。非参数同胞对连锁分析 方差分量连锁分析将用于确定可能包含基因的区域 对于八个最好的地区确定的证据的联系，八个新的标记将是 基因分型以缩小候选区域。该项目的成功完成将导致初始阶段 在定位赋予DR易感性的新基因中，这些基因产物的表征将 提高我们对DR发病机制的认识，并导致新的预防和治疗药物的开发。 治疗策略此外，DR的遗传标记的可用性将允许早期识别 有风险的患者，应作为强化血糖和血压控制的目标。

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.