Identification of quantitative trait loci for glucose honteostasis - The insulin resistance atherosclerosis study (IRAS) family study
Identification of quantitative trait loci for glucose honteostasis - The insulin resistance atherosclerosis study (IRAS) family study
复制标题
DOI：
10.2337/diabetes.53.7.1866
复制
发表时间：
2004-07-01
期刊：
影响因子：
7.7
通讯作者：
Bergmans, RN
中科院分区：
文献类型：
--
作者：
Rich, SS;Bowden, DW;Bergmans, RN
遗传和环境决定因素在胰岛素抵抗和β细胞功能中起关键作用。一个维持葡萄糖耐量的复杂反馈系统模型已经被开发出来，它反映了血糖在狭窄的生理限制内的约束。“葡萄糖稳态”模型由胰岛素敏感性（S-I）、葡萄糖处置（S-G）、胰岛素对葡萄糖的急性反应（AIR(G)）和处置指数（DI）描述。相对而言，我们对葡萄糖稳态表型的遗传基础及其与糖尿病和动脉粥样硬化性心血管疾病风险的关系知之甚少。作为IRAS家族研究的一部分，在非糖尿病受试者中对非裔美国人（n = 21）和西班牙裔（n = 45）大家庭进行了葡萄糖稳态表型的基因组扫描。在非裔美国人家庭中，在81 cM处，D11S2371和D11S2002之间存在显著的DI连锁（LOD = 3.21）；在非裔美国人和西班牙裔家庭的联合样本中，在11号染色体上的GATA117D01 （140 cM）处存在明显的DI连锁（LOD = 2.21）。还观察到西班牙裔家庭的S-I （LOD 2.28，在D15S822和GTTTT001之间）和非裔美国家庭的AIR(G) （LOD = 2.73，在D4S1625和D4S1629之间；12号染色体上PAH（苯丙氨酸羟化酶）的LOD = 2.56）的连锁证据。这些结果为今后数量性状位点的定位克隆提供了理论依据。识别这些区域的基因将有助于深入了解代谢综合征和糖尿病的本质，并促进开发更有效的治疗方法，以预防和治疗糖尿病和其他与糖代谢紊乱相关的疾病。
Genetic and environmental determinants play critical roles in insulin resistance and beta-cell function. A model of the complex feedback system for maintenance of glucose tolerance has been developed that reflects the constraint of glycemia within narrow physiologic limits. The "glucose homeostasis" model is described by insulin sensitivity (S-I), glucose disposition (S-G), acute insulin response to glucose (AIR(G)), and disposition index (DI). Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes and atherosclerotic cardiovascular disease. A genome scan for glucose homeostasis phenotypes in nondiabetic subjects has been carried out in African-American (n = 21) and Hispanic (n = 45) extended families as part of the IRAS Family Study. In African-American families, there was significant evidence for linkage of DI between D11S2371 and D11S2002 (logarithm of odds [LOD] = 3.21) at 81 cM, and in the combined sample of African-American and Hispanic families, there was evidence at GATA117D01 (140 cM) on chromosome 11 (LOD = 2.21). Evidence of linkage was also observed for, S-I in Hispanic (LOD 2.28, between D15S822 and GTTTT001) and AIR(G) in African-American families (LOD = 2.73, between D4S1625 and D4S1629; and LOD = 2.56 at PAH (phenylalanine hydroxylase) on chromosome 12). These results provide impetus for future positional cloning of quantitative trait loci (QTLs). Identifying genes in these regions should provide insight into the nature of the metabolic syndrome and diabetes, and facilitate the development of more effective therapies for prevention and treatment of diabetes and other diseases associated with disordered glucose metabolism.