Systematic search for single nucleotide polymorphisms in the insulin gene:Evidence for a high frequency of-23T -> A in Japanese subjects

It has recently been shown that the A/A genotype at g.-23 of the insulin ge ne correlates with impaired insulin secretion in response to body weight ga in in subjects of European descent. To examine whether there are single nuc leotide polymorphisms (SNPs) in the insulin gene associated with type 2 dia betes, all exons with their flanking sequences for 113 Japanese type 2 diab etic patients and 99 nondiabetic control subjects were analyzed using PCR d irect sequencing. We have only found g.-23T -->A, 806G -->C, 1128 -->C, and 1141A -->C, which have previously been reported in alpha (A-C-C-C) and bet a (T-G-T-A) alleles. The allele frequency of -23T -->A in control Japanese subjects was 97.4%, whereas that in Europeans is about 30%. The A/A genotyp e was found in 94 of 99 Japanese subjects (94.9%) and the allele frequencie s of 806G -->C, 1128 -->C, and 1141A -->C were all 96.5%. The estimated hap lotype frequencies were (A-C-C-C) (96.0%), (T-G-T-A) (2.0%), (A-G-T-A) (1.5 %), and (T-C-C-C) (0.5%). No association of these SNPs or haplotypes with t ype 2 diabetes was evident. Thus, the A/A genotype at the g.-23 of insulin gene was generally high in Japanese subjects, which could account for the f act that they typically secrete lower levels of insulin. (C) 2001 Academic Press.