title: Missense mutation of amylin gene (S20G) in Japanese NIDDM patients.
abstract: Many studies suggest that amylin, which is cosecreted with insulin from islet beta-cells, is a biologically active peptide and modulates plasma glucose levels. We therefore scanned the amylin gene for mutations in 294 Japanese NIDDM patients by single-strand conformational polymorphism, and we found a single heterozygous missense mutation (Ser-->Gly at position 20: S20G mutation) in 12 NIDDM patients (frequency 4.1%). None of the 187 nondiabetic subjects or 59 IDDM patients had the mutation. Of 12 patients carrying the mutation, 8 were diagnosed as having NIDDM at a relatively early age (< or = 35 years), and they had severe diabetes and strong family histories of late-onset NIDDM. On the other hand, the remaining four patients were diagnosed as having NIDDM after age 51, and they had mild diabetes without family histories of diabetes. In high-performance liquid chromatography analysis, a small amount (16%) of amylin immunoreactivity appeared in the position corresponding to normal amylin and a much larger amount (84%) appeared in the position corresponding to mutant amylin. These findings suggest that the S20G mutation of the amylin gene may play a partial role in the pathogenesis of early-onset NIDDM in the Japanese population and may also provide an important model to investigate the true physiological action of amylin.
authors.affiliation: First Department of Medicine, Wakayama University of Medical Science, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakagashira
authors.forename: T
authors.initials: T
authors.lastname: Sanke
authors.forename: T
authors.initials: T
authors.lastname: Hanabusa
authors.forename: H
authors.initials: H
authors.lastname: Shimomura
authors.forename: S
authors.initials: S
authors.lastname: Ohagi
authors.forename: K Y
authors.initials: KY
authors.lastname: Kumagaye
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Nanjo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000682:Amyloid / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D000682:Amyloid; D017931:DNA Primers; D058228:Islet Amyloid Polypeptide