1986 年 29 巻 1 号 p. 77-80
Polymorphism in the 5' flanking region of the human insulin gene in 134 unrelated Japanese subjects 73 with noninsulin-dependent diabetes mellitus (NIDDM) 16 with insulin-dependent diabetes mellitus (IDDM) and 45 controls was investigated using the Southern blot hybridizationmethod. DNA isolated from peripheral blood leukocytes was digested with the restriction enzymes Sac I, Pst I and/or Bgl II and hybridized with a 32P-labeled insuin-DNA-specific probe. The specific probe was a 5' flanking BamHI-BgI II fragment or a Pst I fragment, which contained the polymorphic locus. The results were classified into three groups according the size of the hybridized fragment. The Sac I (Pst I) fragment of the class 1 allele was 5.9 (1.1)±0.3kb in length, the Sac I (Pst I) fragment of the class 2 allele was 6.6 (1.8)±0.3kb in length, and the Sac I (Pst I) fragment of the class 3 allele was greater than 7.0 (2.2) kb in length.
The allelic frequency of classes 2 and 3, in total 268 alleles, was 5.6%, while in 116 alleles of NIDDM it was 8.2%. The value was lower than in Caucasians and U. S. blacks, and the results suggested that the 5' flanking insertion was not a genetic marker of the majority of NIDDM in the Japanese. As NIDDM is a heterogeneos disease, further detailed analysis is needed. When the frequency according the family history of diabetes mellitus, obesity and age at onset was compared the allelic frequency of classes 2 and 3 in NIDDM with a family history without obesity tended to be higher than others with NIDDM (P=0.013), and the frequency in NIDDM whose onset was at the age of 39 or less tended to be lower than those whose onset was at 40 or move (P=0.062). On the other hand, the frequency in IDDM was 0%(versus NIDDM P=0.095). These results suggested that we could not completely, exclude the significance of the insertion in NIDDM and possibility of without the insertion related with IDDM.