GENES FOR NON-INSULIN-DEPENDENT DIABETES MELLITUS

糖尿病是一组以胰岛素绝对或相对缺乏引起的高血糖为特征的代谢紊乱。糖尿病的慢性高血糖与长期的组织损伤有关，尤其是眼睛、肾脏、神经、心脏和血管。2型或非胰岛素依赖型糖尿病是最常见的糖尿病，在美国约有1500万人受到影响。遗传因素在2型糖尿病的发展中起着重要作用，本应用程序的总体目标是确定导致2型糖尿病的基因，然后确定它们如何促进这种疾病的发病机制。在目前的资助期内，在这项资助的支持下进行的研究表明，使用没有父母的受影响的兄弟姐妹对进行连锁研究可用于定位2型糖尿病的基因。我们绘制了墨西哥裔美国人2型糖尿病的主要易感基因（基因符号NIDDM1），该基因可能占该人群2型糖尿病家族聚类的30%，位于标记D2S125-D2S140区域。我们的研究还提供了其他影响小于NIDDM1的易感基因的证据。这是芝加哥大学、休斯顿德克萨斯大学健康科学中心和弗吉尼亚梅森研究中心的研究人员合作研究的继续，目的是确定2型糖尿病的基因。第一个资助周期的目的是绘制2型糖尿病的基因图谱。我们已经在实现这一目标方面取得了重大进展，现在建议从遗传连锁研究自然过渡到NIDDM1和其他2型糖尿病基因的鉴定和功能表征。在芝加哥大学进行的研究将集中在NIDDM1上，而在休斯顿的德克萨斯大学健康科学中心和弗吉尼亚梅森研究中心进行的研究将涉及含有假定的2型糖尿病基因的其他区域。2型糖尿病基因的鉴定和表征将有助于更好地了解这种疾病的分子基础，从而为基于潜在分子缺陷性质的预防和治疗新方法提供基础。

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from an absolute or relative deficiency of insulin. The chronic hyperglycemia of diabetes is associated with long-term tissue damage, especially of the eyes, kidneys, nerves, heart and blood vessels. Type 2 or non-insulin-dependent diabetes mellitus is the most common form of diabetes, affecting about 15 million people in the United States. Genetic factors play an important role in the development of type 2 diabetes and the overall aim of this application is to identify the genes that are responsible for type 2 diabetes and then to determine how they contribute to the pathogenesis of this disorder. During the present funding period, research carried out under the auspices of this grant has shown that linkage studies using affected sib pairs without parents can be used to localize genes for type 2 diabetes. We have mapped the major type 2 diabetes susceptibility gene in Mexican Americans (gene symbol, NIDDM1), a gene which may account for 30 percent of the familial clustering of type 2 diabetes in this population, to the region of the markers D2S125-D2S140. Our studies also provided evidence for other susceptibility genes of smaller effect than NIDDM1. This is a continuation of collaborative studies between investigators at The University of Chicago, the University of Texas Health Science Center at Houston and Virginia Mason Research Center to identify genes for type 2 diabetes. The aim in the first funding cycle was to map the genes for type 2 diabetes. We have made major progress toward reaching this goal and now propose to make the natural transition from genetic linkage studies to identification and functional characterization of NIDDM1 and other type 2 diabetes genes. Studies being carried out at the University of Chicago will focus on NIDDM1 whereas those at the University of Texas Health Science Center at Houston and Virginia Mason Research Center will involve other regions containing putative type 2 diabetes genes. The identification and characterization of the genes for type 2 diabetes will lead to a better understanding of the molecular basis of this disorder, thereby providing the basis for new approaches for prevention and treatment based on the nature of the underlying molecular defect.