IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
2007 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 8, no 6, 503-512 p.Article in journal (Refereed) Published
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 10-13) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 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.
Place, publisher, year, edition, pages
2007. Vol. 8, no 6, 503-512 p.
Adolescent, Adult, Autoantibodies/blood/*immunology, Case-Control Studies, Child, Child; Preschool, Diabetes Mellitus; Type 1/*genetics/*immunology/metabolism, Female, GTP-Binding Proteins/*genetics/metabolism, Humans, Infant, Infant; Newborn, Male, Polymorphism; Single Nucleotide, Sweden
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-14463DOI: 10.1038/sj.gene.6364413PubMedID: 17641683OAI: oai:DiVA.org:uu-14463DiVA: diva2:42233