Abstract Title:

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

Abstract Source:

Genes Immun. 2007 Sep ;8(6):503-12. Epub 2007 Jul 19. PMID: 17641683

Abstract Author(s):

J-H Shin, M Janer, B McNeney, S Blay, K Deutsch, C B Sanjeevi, I Kockum, A Lernmark, J Graham, , , Hans Arnqvist, Elizabeth Björck, Jan Eriksson, Lennarth Nyström, Lars Olof Ohlson, Bengt Scherstén, Jan Ostman, M Aili, L E Bååth, E Carlsson, H Edenwall, G Forsander, B W Granström, I Gustavsson, R Hanås, L Hellenberg, H Hellgren, E Holmberg, H Hörnell, Sten-A Ivarsson, C Johansson, G Jonsell, K Kockum, B Lindblad, A Lindh, J Ludvigsson, U Myrdal, J Neiderud, K Segnestam, S Sjöblad, L Skogsberg, L Strömberg, U Ståhle, B Thalme, K Tullus, T Tuvemo, M Wallensteen, O Westphal, J Aman

Article Affiliation:

Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada.

Abstract:

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 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 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.

Study Type : Human Study

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