Masuda K, Yano H, Miura T, Morimoto M, Kitano N, Seino Y
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan.
Endocr J. 1994 Feb;41(1):71-4. doi: 10.1507/endocrj.41.71.
The gene encoding Proinsulin Kyoto has been isolated and characterized by DNA sequencing, indicating that the molecular basis of the disorder is a G-T point mutation in the insulin gene which creates a Hind III site. In addition, in the 3'-untranslated region of the mutant insulin gene, a Pst I site negative, alpha type allele was found, and in the normal gene, a Pst I site positive, beta type allele was found. In order to clarify the frequency of the mutation and to determine whether this mutation is associated with diabetes mellitus or not, we have investigated Hind III polymorphism in 91 normal Japanese subjects and patients with IDDM and NIDDM. No cases with the Proinsulin Kyoto gene were found among the subjects examined. Secondly, to determine whether this alpha type allele is associated with DM in Japanese, we investigated Pst I polymorphism in the same subjects. The frequencies of the alpha type and beta type alleles were 92% and 8%, respectively. No significant difference in genotypic frequency was found among normal, NIDDM, and IDDM. We conclude that the Proinsulin Kyoto gene is not a common cause of DM and the occurrence of the alpha type insulin gene in Japanese diabetes is more frequent than in other races, so this Pst I polymorphism is not a marker for diabetes mellitus in Japanese.
编码京都胰岛素原的基因已通过DNA测序进行了分离和鉴定，表明该疾病的分子基础是胰岛素基因中的一个G-T点突变，该突变产生了一个Hind III位点。此外，在突变胰岛素基因的3'-非翻译区，发现了一个Pst I位点阴性的α型等位基因，而在正常基因中，发现了一个Pst I位点阳性的β型等位基因。为了阐明该突变的频率并确定此突变是否与糖尿病相关，我们对91名正常日本受试者以及IDDM和NIDDM患者进行了Hind III多态性研究。在所检查的受试者中未发现携带京都胰岛素原基因的病例。其次，为了确定这种α型等位基因在日本人中是否与糖尿病相关，我们对相同受试者进行了Pst I多态性研究。α型和β型等位基因的频率分别为92%和8%。在正常、NIDDM和IDDM患者中，基因型频率未发现显著差异。我们得出结论，京都胰岛素原基因不是糖尿病的常见病因，并且α型胰岛素基因在日本糖尿病患者中的出现频率高于其他种族，因此这种Pst I多态性不是日本人糖尿病的标志物。
