Cox N J, Epstein P A, Spielman R S
Department of Medicine, University of Chicago, Illinois.
Diabetes. 1989 May;38(5):653-8. doi: 10.2337/diab.38.5.653.
Twenty Black families in which at least two siblings had non-insulin-dependent diabetes mellitus (NIDDM) were typed for restriction-fragment-length polymorphisms at the insulin (INS), insulin-receptor (INSR), and HLA-DR beta loci. Evidence for linkage between NIDDM and these loci was assessed with various genetic models for the transmission of NIDDM and with the affected-sib-pair approach, which does not require assumptions concerning a genetic model for NIDDM. Tight linkage between NIDDM and any of the loci was unlikely under all of the genetic models examined. Similarly, for all three of the loci, the distribution of affected sib pairs sharing 2, 1, or 0 genes identical by descent was not significantly different from (and was very similar to) that expected if the locus were unrelated to disease susceptibility. There was no evidence for linkage heterogeneity for any of the loci when families were grouped according to obesity or age at onset or when considering families individually. We conclude that the INS and INSR loci can be ruled out as major susceptibility loci for NIDDM in most Black families segregating this disorder, but we recognize that defects at either of these loci may cause or contribute to NIDDM in some patients. In addition, it is possible that variation at the INS and/or INSR loci may contribute to NIDDM susceptibility by modifying susceptibility due primarily to another major gene(s) or as part of an overall polygenic component to NIDDM.
对20个黑人家庭进行了胰岛素（INS）、胰岛素受体（INSR）和HLA - DRβ基因座的限制性片段长度多态性分型，这些家庭中至少有两个兄弟姐妹患有非胰岛素依赖型糖尿病（NIDDM）。采用NIDDM遗传传递的各种遗传模型以及患病同胞对法评估NIDDM与这些基因座之间的连锁证据，患病同胞对法不需要关于NIDDM遗传模型的假设。在所研究的所有遗传模型下，NIDDM与任何一个基因座之间紧密连锁的可能性都不大。同样，对于所有这三个基因座，按血缘关系共享2个、1个或0个相同基因的患病同胞对的分布与该基因座与疾病易感性无关时预期的分布没有显著差异（且非常相似）。当根据肥胖或发病年龄对家庭进行分组或单独考虑各个家庭时，没有证据表明任何一个基因座存在连锁异质性。我们得出结论，在大多数患有这种疾病的黑人家庭中，可以排除INS和INSR基因座作为NIDDM的主要易感基因座，但我们认识到这两个基因座中的任何一个缺陷都可能在某些患者中导致或促成NIDDM。此外，INS和/或INSR基因座的变异可能主要通过修饰主要由另一个主要基因引起的易感性或作为NIDDM整体多基因成分的一部分来促成NIDDM易感性。
