Elbein S C, Borecki I, Corsetti L, Fajans S S, Hansen A T, Nerup J, Province M, Permutt M A
VAMC, Salt Lake City, Utah.
Diabetologia. 1987 Aug;30(8):641-7. doi: 10.1007/BF00277322.
The cloning of the insulin receptor cDNA has permitted the definition of restriction fragment length polymorphisms at that locus. These polymorphisms were used to study the role of the insulin receptor in four pedigrees with maturity onset diabetes of the young through linkage analyses. When each pedigree was individually analysed, no linkage was demonstrated in the two larger pedigrees, implying that an insulin receptor defect was not responsible for the predisposition to diabetes in these pedigrees. One of these pedigrees was known to be hypoinsulinaemic, while insulin levels were unavailable in the second pedigree. In the two smaller pedigrees, however, a single haplotype cosegregated with diabetes. One of these pedigrees is known to be hyperinsulinaemic. The small size of the pedigrees which demonstrated cosegregation precluded statistical proof of linkage. Nonetheless, the presence of an uncommon insertional polymorphism which cosegregated with diabetes in both pedigrees was improbable and suggested that this insertion could be responsible for diabetes in these families. This study thus may be additional evidence for heterogeneity in maturity onset diabetes of the young. For the two larger pedigrees, the insulin gene and HLA region have already been eliminated as genetic markers. This study provides data which eliminate a third candidate gene in these two pedigrees.
胰岛素受体cDNA的克隆使得能够确定该位点的限制性片段长度多态性。这些多态性被用于通过连锁分析研究胰岛素受体在四个青年发病型成年糖尿病家系中的作用。对每个家系单独进行分析时，在两个较大的家系中未显示连锁关系，这意味着胰岛素受体缺陷并非这些家系中糖尿病易感性的原因。其中一个家系已知存在低胰岛素血症，而第二个家系的胰岛素水平未知。然而，在两个较小的家系中，单一单倍型与糖尿病共分离。其中一个家系已知存在高胰岛素血症。显示共分离的家系规模较小，无法进行连锁关系的统计学验证。尽管如此，两个家系中均存在与糖尿病共分离的罕见插入多态性，这种情况不太可能，提示该插入可能是这些家族中糖尿病的病因。因此，本研究可能是青年发病型成年糖尿病存在异质性的又一证据。对于两个较大的家系，胰岛素基因和HLA区域已被排除作为遗传标记。本研究提供的数据排除了这两个家系中的第三个候选基因。
