1. IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.
- Author
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Shin JH, Janer M, McNeney B, Blay S, Deutsch K, Sanjeevi CB, Kockum I, Lernmark A, Graham J, Arnqvist H, Björck E, Eriksson J, Nyström L, Ohlson LO, Scherstén B, Ostman J, Aili M, Bååth LE, Carlsson E, Edenwall H, Forsander G, Granström BW, Gustavsson I, Hanås R, Hellenberg L, Hellgren H, Holmberg E, Hörnell H, Ivarsson SA, Johansson C, Jonsell G, Kockum K, Lindblad B, Lindh A, Ludvigsson J, Myrdal U, Neiderud J, Segnestam K, Sjöblad S, Skogsberg L, Strömberg L, Ståhle U, Thalme B, Tullus K, Tuvemo T, Wallensteen M, Westphal O, and Aman J
- Subjects
- Adolescent, Adult, Autoantibodies blood, Case-Control Studies, Child, Child, Preschool, Diabetes Mellitus, Type 1 metabolism, Female, GTP-Binding Proteins metabolism, Humans, Infant, Infant, Newborn, Male, Polymorphism, Single Nucleotide, Sweden, Autoantibodies immunology, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 immunology, GTP-Binding Proteins genetics
- 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.
- Published
- 2007
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