论文部分内容阅读
2型糖尿病(T2DM)是由于胰岛素抵抗和β细胞分泌缺陷导致高血糖的一种复杂多基因疾病。遗传因素在T2DM的发生发展中起着重要的作用,其遗传率估计为70%～80%。鉴定2型糖尿病基因将有助于阐明其发病机制,发展更好的诊断、预防和治疗策略。2型糖尿病易感基因的鉴定方法主要有候选基因关联研究和全基因组连锁分析。有3种类型的候选基因:功能候选基因、图位候选基因和表达候选基因。虽然许多候选基因与T2DM的关联分析已经进行,但多数都没有得到一致的重复,过氧化物酶体增殖物激活受-γ体和β-细胞ATP敏感性钾通道基因是目前最好重复的基因。迄今为止,T2DM的全基因组扫描已在20多个不同的群体中进行,包括欧洲人、美国白人、墨西哥裔美国人、美国本地印度人、非洲裔美国人和亚洲人,这些研究鉴定了一些与T2DM相关的QTLs区域。与T2DM显著和证实连锁的区域包括1q25、2q37、3q28、3p24、6q22、8p23、10q26、12q24、18p11、20q13等,与T2DM提示连锁的区域有1q42、2p21、2q24、4q34、5q13、5q31、7q32、9p24、9q21、10p14、11p13、11q13、12q15、14q23、20p12、Xq23等。鉴定这些区域的T2DMQTLs基因及其作用机制是未来的主要挑战。把DNA微阵列和蛋白质组学技术结合起来应用于传统的连锁分析和关联研究,研究基因-基因间、基因-环境间的互作和多个基因对T2DM的加性效应和综合作用,进一步加强国际协作,T2DM的遗传机制可望在不远的将来得到阐明。本文总结了2型糖尿病基因鉴定的现状,重点在一些得到重复的区域和未来的展望。
Type 2 diabetes (T2DM) is a complex polygenic disease that leads to hyperglycemia due to insulin resistance and defective beta cell secretion. Genetic factors in the occurrence and development of T2DM plays an important role in the heritability estimated at 70% to 80%. Identification of type 2 diabetes genes will help elucidate its pathogenesis and develop better strategies for diagnosis, prevention and treatment. Methods of identification of type 2 diabetes susceptibility genes include candidate gene association studies and genome-wide linkage analysis. There are 3 types of candidate genes: function candidate genes, map candidate genes and expression candidate genes. Although many candidate genes have been linked to T2DM, most have not been consistently duplicated and peroxisome proliferator-activated beta-cell ATP-sensitive potassium channel genes are by far the best-repeated genes . To date, genome-wide scans of T2DM have been performed in more than 20 different populations, including Europeans, White Americans, Mexican Americans, Native American Indians, African Americans and Asians. These studies identified a number of T2DM-related QTLs region. Areas markedly and positively linked to T2DM include 1q25, 2q37, 3q28, 3p24, 6q22, 8p23, 10q26, 12q24, 18p11, 20q13, etc. The regions linked to the T2DM hints are 1q42,2p21,2q24,4q34,5q13,5q31,7q32 , 9p24, 9q21, 10p14, 11p13, 11q13, 12q15, 14q23, 20p12, Xq23 and the like. Identification of T2DMQTLs genes in these regions and their mechanisms of action are major challenges in the future. The combination of DNA microarray and proteomics technology used in traditional linkage analysis and association studies to study the gene - gene, gene - environment interaction and multiple genes on the additive effect of T2DM and the combined effect, to further strengthen International cooperation, T2DM genetic mechanism is expected to be clarified in the near future. This article summarizes the current status of genotyping of type 2 diabetes, focusing on areas that are duplicated and future prospects.