Polymorphism in the 5'-flanking region of the human insulin gene in 149 unrelated Japanese subjects [77 with non-insulin-dependent diabetes mellitus (NIDDM), 17 with insulin-dependent diabetes mellitus (IDDM), and 55 controls] was analyzed with Southern blot hybridization. We used the size of the hybridized fragments to classify the locus into three groups according to Bell's method (a short, class 1 allele averaging 570 base pairs; an intermediate-size, class 2 allele averaging 1320 base pairs, and a long, class 3 allele averaging 2470 base pairs in size). The allelic frequency of classes 2 and 3 in 298 alleles was 5.0% and in the 146 alleles of NIDDM, 7.8%. The value is lower than in Caucasians, American Blacks, and Pima Indians, and the results suggest that the 5'-flanking insertion is not a genetic marker in most NIDDM patients who are Japanese. However, the frequency of the 5'-flanking insertion in those who were not obese and had a family history of diabetes was higher than that of other NIDDM patients (P = .013), and the frequency in NIDDM patients with onset of diabetes at age ≤39 yr was lower than those whose onset was at age ≥40 yr (P = .053). As NIDDM is a heterogeneous disorder, further analysis is needed. These results suggest that we cannot completely exclude the meaning of the insertion in NIDDM. On the other hand, the frequency in IDDM was 0%, lower than in NIDDM (P = .094). Because the number of subjects studied was small, this result is speculative.

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