S20G mutation of the amylin gene is associated with Type II diabetes in Japanese. Study Group of Comprehensive Analysis of Genetic Factors in Diabetes Mellitus.

Amylin is a unique constituent peptide of the amyloid deposits found in pancreatic islets in many patients with Type II (non-insulin-dependent) diabetes mellitus. A previous study suggested that a missense mutation at amino acid 20 (AGCSer to GGCGlY), the S20G mutation, could play a role in the pathogenesis of early-onset Type II diabetes in Japanese people. In order to determine the association between the S20G mutation and Type II diabetes in the Japanese population, we did a large scale screening for the mutation in randomly selected Type II diabetic patients and non-diabetic control subjects. We examined 1,538 unrelated patients with Type II diabetes and 1,108 non-diabetic control subjects recruited from 9 university hospitals and their affiliated hospitals in 7 prefectures in Japan. The presence or absence of the S20G mutation of the amylin gene was assessed by direct DNA sequencing or MspI RFLP analysis of the amplified polymerase chain reaction products of exon 3. The S20G mutation was found in 40 (2.6%) and 9 (0.8%) of the subjects in the Type II diabetic and the non-diabetic control groups, respectively, all present in the heterozygous state. The frequency of individuals with the S20G mutation is different between the two groups (p = 0.0007). These data suggest that the S20G mutation in the amylin gene is associated with increased risk of development of Type II diabetes in Japanese.