Low frequency of the large insertion in the human insulin gene in Japanese.

We have studied the restriction fragment-length polymorphism in the 5'-flanking region of the human insulin gene in 47 nondiabetic Japanese subjects and in 52 subjects with non-insulin-dependent diabetes (NIDDM) to elucidate the ethnic variation of the genetic polymorphism and its relationship with NIDDM. Allelic frequencies in the nondiabetic subjects were 0.957 in class 1 (Bgl l fragments of 2800 +/- 300 bp), 0 in class 2 (fragments of 3500 +/- 300 bp), and 0.043 in class 3 (fragments of greater than 3900 bp with a mean of 4500 bp). Corresponding frequencies in the NIDDM subjects were 0.962, 0, and 0.038, respectively. Four subjects with NIDDM who had the class 3 allele did not exhibit any particular clinical characteristics compared with the rest of the patients. Thus, the class 3 allele or the large insertion of the human insulin gene is much less frequent in Japanese than reported in other races, including Caucasians, and this class of allele is not associated with NIDDM in Japanese. Ethnic homogeneity is, thus, important in the analysis and interpretation of the genetic polymorphism.