GENETICS OF DIABETIC RETINOPATHY

说明：（申请人的摘要）糖尿病视网膜病变基本上 2型糖尿病的发病率，是一个强有力的 预测糖尿病患者随后的，通常是早期的死亡率。 2型糖尿病的易感性长期以来一直被认为是有一个 重要的遗传成分。糖尿病不仅聚集在 家庭，但它的并发症也是如此。初步结果显示， 糖尿病患者的兄弟姐妹患视网膜病变的风险增加8.3倍， 糖尿病，无视网膜病变。很可能糖尿病易感性 等位基因影响疾病的临床进程和 视网膜病变其他基因也可能影响 视网膜病变的易感性，但只有在 糖尿病的发展。为了确定基因的贡献， 糖尿病视网膜病变的因素，1,000名墨西哥裔美国人与2型糖尿病 糖尿病分布在750兄弟姐妹对将接受详细的眼睛 两次检查（间隔2.5年）。检查将包括 立体眼底照相并按标准评分 协议.除了视网膜检查，这些人有 在斯塔尔县正在进行的研究中， 德克萨斯这些表征包括在跨越这些基因的标记处的基因型。 整个基因组的平均距离为8到10厘摩根。所有 在第一轮结束之前，将提供标记数据 视网膜检查。记录以下情况的存在和严重程度 糖尿病视网膜病变在这个同胞对基因型资源和一个 另外一组200名糖尿病患者将 许可：1）确定视网膜病变的同胞对一致性，2） 基于两点和多点的视网膜病变易感位点定位 点同胞对连锁分析，和3）变异的鉴定 通过DNA序列扫描的基因在连接区域的影响， 视网膜病变的存在和发展。最终结果会得到改善 了解迁移的机制和可利用的途径 视网膜病变治疗从姑息性到预防性。

DESCRIPTION: (Applicant's Abstract) Diabetic retinopathy substantially contributes to the morbidity of type 2 diabetes mellitus and is a strong predictor of subsequent, often early, mortality in those with diabetes. Susceptibility to type 2 diabetes has long been known to have a substantial genetic component. Not only does diabetes aggregate in families, but so do its complications. Preliminary results demonstrate an 8.3 fold increased risk for retinopathy in diabetic siblings of a diabetic with no retinopathy. It is likely that diabetes susceptibility alleles impact the clinical courses of the disease and development of retinopathy. It is also plausible that other genes influence susceptibility to retinopathy, but exert their influence only after the development of diabetes. To determine the contribution of genetic factors to diabetic retinopathy, 1,000 Mexican Americans with type 2 diabetes distributed in 750 sibling pairs will undergo detailed eye examinations on 2 occasions (2.5 years apart). Examinations will include stereoscopic fundus photography and scoring according to standard protocols. Except for the retinal examinations, these individuals have been and are being characterized in ongoing studies in Starr County, Texas. These characterization includes genotypes at markers spanning the entire genome at an average distance of 8 to 10 centi-Morgans. All marker data will be available prior to the completion of the first round of retinal examinations. Documentation of the presence and severity of diabetic retinopathy in this sibling pair genotype resource and an additional confirmatory set of 200 individuals with diabetes will permit: 1) Determining the sibling pair concordance for retinopathy, 2) Localizing retinopathy susceptibility loci based on two-point and multi- point sibling pair linkage analysis, and 3) Identification of variation by DNA sequence scanning of genes in linked regions impacting on the presence and development of retinopathy. The end result will be improved understanding of mechanisms and exploitable pathways for moving retinopathy treatment from palliative to preventive.