Pratley R E, Thompson D B, Prochazka M, Baier L, Mott D, Ravussin E, Sakul H, Ehm M G, Burns D K, Foroud T, Garvey W T, Hanson R L, Knowler W C, Bennett P H, Bogardus C
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
J Clin Invest. 1998 Apr 15;101(8):1757-64. doi: 10.1172/JCI1850.
Type 2 diabetes mellitus is a common chronic disease that is thought to have a substantial genetic basis. Identification of the genes responsible has been hampered by the complex nature of the syndrome. Abnormalities in insulin secretion and insulin action predict the development of type 2 diabetes and are, themselves, highly heritable traits. Since fewer genes may contribute to these precursors of type 2 diabetes than to the overall syndrome, such genes may be easier to identify. We, therefore, undertook an autosomal genomic scan to identify loci linked to prediabetic traits in Pima Indians, a population with a high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped at 516 polymorphic microsatellite markers on all 22 autosomes. Linkage analyses were performed using three methods (single-marker, nonparametric multipoint [MAPMAKER/SIBS], and variance components multipoint). These analyses provided evidence for linkage at several chromosomal regions, including 3q21-24 linked to fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma glucose concentration. These results suggest loci that may harbor genes contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These findings must, therefore, be considered tentative until extended in this population or replicated in others.
2型糖尿病是一种常见的慢性病，被认为具有重要的遗传基础。该综合征的复杂性阻碍了对相关基因的识别。胰岛素分泌和胰岛素作用异常预示着2型糖尿病的发生，而且这些异常本身就是高度可遗传的性状。由于导致2型糖尿病这些前驱症状的基因可能比导致整体综合征的基因数量更少，因此这类基因可能更容易识别。因此，我们进行了一项常染色体基因组扫描，以确定与皮马印第安人糖尿病前期性状相关的基因座，该人群中2型糖尿病的患病率很高。对363名非糖尿病皮马印第安人在所有22条常染色体上的516个多态性微卫星标记进行了基因分型。使用三种方法进行连锁分析（单标记法、非参数多点法[MAPMAKER/SIBS]和方差成分多点法）。这些分析为几个染色体区域的连锁提供了证据，包括与空腹血浆胰岛素浓度和体内胰岛素作用相关的3q21 - 24、与空腹血浆胰岛素浓度相关的4p15 - q12、与口服葡萄糖耐量试验期间2小时胰岛素浓度相关的9q21以及与空腹血糖浓度相关的22q12 - 13。这些结果表明，在皮马印第安人中可能存在与2型糖尿病相关的基因座。没有一个连锁的对数优势比（LOD）得分超过3.6（在全基因组扫描中出现的概率为5%）。因此，在该人群中进行扩展研究或在其他人群中重复验证之前，这些发现必须被视为初步结果。
