title: Islet amyloid polypeptide gene promoter polymorphisms are not associated with Type 2 diabetes or with the severity of islet amyloidosis.
abstract: The over-expression of the islet amyloid polypeptide (IAPP) gene could be a causal factor for islet amyloidosis and beta-cell destruction in Type 2 diabetes (T2DM). An IAPP gene promoter polymorphism, IAPP-132G to A, has been associated with T2DM in Spain. To investigate this polymorphism in other cohorts and in relation to therapy, DNA from 425 T2DM and 279 unrelated, non-diabetic UK subjects (ND) and 102 T2DM and 80 ND Finnish subjects was examined. The relationship of amyloid severity (percent amyloid/islet) to prevalence (number of islets affected) and the association of IAPP-132G/A with amyloid was determined in post-mortem pancreas from 38 T2DM subjects. The -132G/A was not associated with T2DM in the UK cohorts (4.5% T2DM; 3.2% ND) or associated with requirement for insulin therapy by 6 years. The mutation was and undetected in the Finnish samples but a new variant, -166T/C, was identified in 2 Finnish T2DM subjects. -132G/A was found in 2/38 diabetic, amyloid-containing and 3/19 ND, amyloid-free subjects. The islet amyloid severity was linearly correlated with the prevalence in T2DM. The IAPP-132G/A promoter polymorphism is not associated with T2DM, a requirement for insulin therapy or with the degree of islet amyloidosis in cohorts from the UK or Finland.
authors.affiliation: Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LJ, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Esapa
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Moffitt
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.forename: Catherine M
authors.initials: CM
authors.lastname: McNamara
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Levy
authors.forename: Marku
authors.initials: M
authors.lastname: Laakso
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
authors.forename: Anne
authors.initials: A
authors.lastname: Clark
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004739:England; D005387:Finland; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010182:Pancreatic Diseases / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide