title: Apolipoprotein E genotype, islet amyloid deposition and severity of Type 2 diabetes.
abstract: Islet amyloid is found in 90% of patients with Type 2 (non-insulin-dependent) diabetes at post-mortem. More extensive amyloidosis is associated with decreased islet function and requirement for insulin therapy. Severity of cerebral amyloidosis in Alzheimer's disease (AD) is increased in subjects with the apolipoprotein E (ApoE) epsilon 4 allele. To determine if ApoE genotype was associated with severity of islet amyloidosis and diabetes, samples were genotyped from 32 specimens of post-mortem pancreas and from patients classified by disease progression. DNA was extracted from blood samples from Caucasian patients diagnosed with Type 2 diabetes, at age >40 years, classified according to disease progression: group 1 on oral therapy for at least 10 years from diagnosis, (n=147) and group 2, requiring insulin within 6 years from diagnosis, (n=187). ApoE genotype was determined by restriction-fragment length polymorphism analysis. DNA in pancreatic extracts (23 diabetic; 9 non-diabetic subjects) showed no association of ApoE polymorphisms with either degree of islet amyloidosis or disease severity. The distributions of ApoE epsilon 2, epsilon 3 and epsilon 4 were similar in both clinical patient groups and in the non-diabetic group and unrelated to progression of disease. It is unlikely that the common polymorphisms for the ApoE gene are linked to amyloid formation or progression of islet dysfunction in Type 2 diabetes.
authors.affiliation: Diabetes Research Laboratories, Oxford Centre for Diabetes Endocrinology and Metabolism, Radcliffe Infirmary, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Powell
authors.forename: H
authors.initials: H
authors.lastname: Maksoud
authors.forename: S B P
authors.initials: SB
authors.lastname: Chargé
authors.forename: J H
authors.initials: JH
authors.lastname: Moffitt
authors.forename: M
authors.initials: M
authors.lastname: Desai
authors.forename: R L
authors.initials: RL
authors.lastname: Da Silva Fihlo
authors.forename: A T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: I M
authors.initials: IM
authors.lastname: Stratton
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
authors.forename: J C
authors.initials: JC
authors.lastname: Levy
authors.forename: A
authors.initials: A
authors.lastname: Clark
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000682:Amyloid / Q000502:physiology*; D000686:Amyloidosis / Q000150:complications / Q000235:genetics* / Q000401:mortality; D001057:Apolipoproteins E / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D044465:White People
chemical_list: D000682:Amyloid; D001057:Apolipoproteins E; D058228:Islet Amyloid Polypeptide