Elbein S C, Hoffman M D, Mayorga R A, Barrett K L, Leppert M, Hasstedt S
Division of Endocrinology, Diabetes and Metabolism, Department of Veterans Affairs Medical Center and University of Utah, Salt Lake City, USA.
Metabolism. 1997 Jan;46(1):48-52. doi: 10.1016/s0026-0495(97)90166-9.
Non-insulin-dependent diabetes mellitus (NIDDM) has been viewed as genetically and physiologically distinct from insulin-dependent diabetes mellitus (IDDM), yet many of the recently suggested IDDM susceptibility loci are likely to increase the risk of diabetes through nonautoimmune mechanisms. To test the hypothesis that the IDDM susceptibility loci include important NIDDM susceptibility loci, we tested the linkage of 14 putative susceptibility regions with NIDDM among families and sibling pairs of Northern European descent. All regions were tested with highly informative microsatellite (simple tandem repeat) polymorphisms in up to 166 affected individuals from 42 families using both parametric and nonparametric methods (149 pairs for sibling pair analyses). We found no evidence for linkage to the majority of loci, including loci that appeared to be linked to IDDM in more than one study. We report some evidence for shared susceptibility for regions on chromosomes 1, 2, and 6. The best evidence based on multilocus affected pedigree member (APM) analysis of markers near D1S191 suggested linkage at P value .0001. This region has not yet been confirmed as an IDDM locus, and our analyses could represent a false-positive result. The role of these three regions will only be clarified by testing in additional families. In combination with other investigations in our laboratory for chromosome 11 susceptibility regions, our data generally do not provide convincing evidence that IDDM and NIDDM share common genetic factors among families of Northern European descent with ascertainment of two or more NIDDM siblings.
非胰岛素依赖型糖尿病（NIDDM）在遗传和生理方面被认为与胰岛素依赖型糖尿病（IDDM）不同，然而，最近提出的许多IDDM易感基因座可能通过非自身免疫机制增加患糖尿病的风险。为了检验IDDM易感基因座包括重要的NIDDM易感基因座这一假设，我们在北欧血统的家族和同胞对中测试了14个假定的易感区域与NIDDM的连锁关系。使用参数法和非参数法，在来自42个家族的多达166名受影响个体中，用信息丰富的微卫星（简单串联重复）多态性对所有区域进行了检测（同胞对分析用了149对）。我们没有发现与大多数基因座连锁的证据，包括在不止一项研究中似乎与IDDM连锁的基因座。我们报告了一些关于1号、2号和6号染色体区域存在共同易感性的证据。基于对D1S191附近标记的多位点受累家系成员（APM）分析，最有力的证据表明连锁的P值为0.0001。该区域尚未被确认为IDDM基因座，我们的分析可能代表假阳性结果。只有通过在更多家族中进行检测，才能阐明这三个区域的作用。结合我们实验室对11号染色体易感区域的其他研究，我们的数据总体上没有提供令人信服的证据，表明在确定有两个或更多NIDDM同胞的北欧血统家族中，IDDM和NIDDM共享共同的遗传因素。
