GENETICS OF DIABETIC RETINOPATHY

描述：(申请人摘要)实质性糖尿病视网膜病变 导致2型糖尿病的发病率，是一种强烈的 糖尿病患者随后死亡的预测指标，通常是早期死亡。 对2型糖尿病的易感性早已为人所知 相当大的遗传成分。糖尿病不仅聚集在 家庭，但它的复杂性也是如此。初步结果表明 糖尿病兄弟姐妹患视网膜病变的风险增加8.3倍 无视网膜病变的糖尿病患者。很可能糖尿病易感性 等位基因影响疾病的临床病程和疾病的发展 视网膜病变。其他基因也有可能影响 易患视网膜病变，但只有在 糖尿病的发展。以确定基因的贡献 糖尿病视网膜病变的因素，1000名墨西哥裔美国人患有2型 分布在750对兄弟姐妹中的糖尿病患者将接受详细的检查 两次考试(相隔两年半)。考试将包括 立体眼底照相及按标准评分 协议。除了视网膜检查，这些人都有 斯塔尔县正在进行的研究中已经和正在进行的研究中， 德克萨斯州。这些特征包括跨越基因的标记的基因类型 整个基因组的平均距离为8到10厘米。全 评分员数据将在第一轮结束前可用 视网膜检查的结果。记录以下情况的存在和严重性 这对兄弟姐妹中的糖尿病视网膜病变的基因资源和 额外的200名糖尿病患者确诊集将 许可：1)确定兄弟姐妹对视网膜病变的一致性，2) 基于两点和多点的视网膜病变易感基因定位 点同胞对连锁分析；3)变异鉴定 通过DNA序列扫描影响基因的连锁区域 视网膜病变的存在和发展。最终结果将会得到改善 了解移动的机制和可开发的路径 视网膜病变治疗从姑息性治疗到预防性治疗。

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.