Objectives: To ascertain the presence of the Ser 20Gly mutation of islet amyloid polypeptide (IAPP) gene and its impact on NIDDM in Chinese.
Methods: In 896 Chinese, 825 were unrelated subjects (NIDDM in 609 and non-diabetics, 216) and 71 were family members of the pedigrees with IAPP gene-Ser 20Gly carrier probands detected from population screening. The mutation was examined by PCR-RFLP MspI digestion in population screening and the results was randomly checked by direct DNA sequencing. Data were analyzed through association as well as linkage approaches.
Results: The Ser20Gly mutation of the IAPP gene was observed in Chinese. It was more prevalent in NIDDM (17 cases, 2.8%) than in non-diabetics (1 cases, 0.5%) (Fisher two-tailed exact P = 0.05). The mutation carrier detected by PCR-RFLP was confirmed to be the A to G point mutation in nucleotide 582 of IAPP gene cDNA encoding the amino acid codon 20. All the mutation carriers detected in population screening were heterozygotes. Analysis of the family members of the 12 NIDDM pedigrees with the IAPP gene Ser20Gly mutation showed that in two families, the mutation was not cosegregated with the affection status. The older was the age of Ser20Gly mutant carrier, the more prevalent was the diabetes in families (P = 0.0001). The highest total lod score of this 12 pedigree was 0.021(theta = 0) in parametric linkage analysis with the model of autosomal dominance with incomplete penetrance.
Conclusion: The Ser20Gly mutation of IAPP gene was present in Chinese. This mutation does not cause monogenic inheritance diabetes, but may be a pathogenetic factor for the development of NIDDM, the complex genetic disease.