title: IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.
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.
authors.affiliation: Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: J-H
authors.initials: JH
authors.lastname: Shin
authors.forename: M
authors.initials: M
authors.lastname: Janer
authors.forename: B
authors.initials: B
authors.lastname: McNeney
authors.forename: S
authors.initials: S
authors.lastname: Blay
authors.forename: K
authors.initials: K
authors.lastname: Deutsch
authors.forename: C B
authors.initials: CB
authors.lastname: Sanjeevi
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: J
authors.initials: J
authors.lastname: Graham
authors.forename: Hans
authors.initials: H
authors.lastname: Arnqvist
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Björck
authors.forename: Jan
authors.initials: J
authors.lastname: Eriksson
authors.forename: Lennarth
authors.initials: L
authors.lastname: Nyström
authors.forename: Lars Olof
authors.initials: LO
authors.lastname: Ohlson
authors.forename: Bengt
authors.initials: B
authors.lastname: Scherstén
authors.forename: Jan
authors.initials: J
authors.lastname: Ostman
authors.forename: M
authors.initials: M
authors.lastname: Aili
authors.forename: L E
authors.initials: LE
authors.lastname: Bååth
authors.forename: E
authors.initials: E
authors.lastname: Carlsson
authors.forename: H
authors.initials: H
authors.lastname: Edenwall
authors.forename: G
authors.initials: G
authors.lastname: Forsander
authors.forename: B W
authors.initials: BW
authors.lastname: Granström
authors.forename: I
authors.initials: I
authors.lastname: Gustavsson
authors.forename: R
authors.initials: R
authors.lastname: Hanås
authors.forename: L
authors.initials: L
authors.lastname: Hellenberg
authors.forename: H
authors.initials: H
authors.lastname: Hellgren
authors.forename: E
authors.initials: E
authors.lastname: Holmberg
authors.forename: H
authors.initials: H
authors.lastname: Hörnell
authors.forename: Sten-A
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: C
authors.initials: C
authors.lastname: Johansson
authors.forename: G
authors.initials: G
authors.lastname: Jonsell
authors.forename: K
authors.initials: K
authors.lastname: Kockum
authors.forename: B
authors.initials: B
authors.lastname: Lindblad
authors.forename: A
authors.initials: A
authors.lastname: Lindh
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: U
authors.initials: U
authors.lastname: Myrdal
authors.forename: J
authors.initials: J
authors.lastname: Neiderud
authors.forename: K
authors.initials: K
authors.lastname: Segnestam
authors.forename: S
authors.initials: S
authors.lastname: Sjöblad
authors.forename: L
authors.initials: L
authors.lastname: Skogsberg
authors.forename: L
authors.initials: L
authors.lastname: Strömberg
authors.forename: U
authors.initials: U
authors.lastname: Ståhle
authors.forename: B
authors.initials: B
authors.lastname: Thalme
authors.forename: K
authors.initials: K
authors.lastname: Tullus
authors.forename: T
authors.initials: T
authors.lastname: Tuvemo
authors.forename: M
authors.initials: M
authors.lastname: Wallensteen
authors.forename: O
authors.initials: O
authors.lastname: Westphal
authors.forename: J
authors.initials: J
authors.lastname: Aman
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013548:Sweden
chemical_list: D001323:Autoantibodies; C484030:GIMAP5 protein, human; C096322:ICA512 autoantibody; D019204:GTP-Binding Proteins