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Åke Lernmark

Principal investigator

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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.

Author

  • JH Shin
  • M Janer
  • B McNeney
  • S Blay
  • K Deutsch
  • CB Sanjeevi
  • I Kockum
  • Åke Lernmark
  • J Graham
  • The Diabetes Incidence in Sweden Study Group
  • The Swedish Childhood Diabetes Study Group

Summary, in English

In a large case-control study of Swedish incident type I diabetes patients and controls, 0–34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 times 10-13) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 times 10-5) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

Department/s

  • Diabetes and Celiac Unit

Publishing year

2007

Language

English

Pages

503-512

Publication/Series

Genes Immun.

Volume

8

Issue

6

Document type

Journal article

Topic

  • Endocrinology and Diabetes

Keywords

  • polyadenylation signal
  • IA-2 autoantibodies
  • GIMAP5
  • type I diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit