title: Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.
abstract: Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.
authors.affiliation: Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, Canada.
authors.forename: Jinko
authors.initials: J
authors.lastname: Graham
authors.forename: William A
authors.initials: WA
authors.lastname: Hagopian
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Lou Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Carani B
authors.initials: CB
authors.lastname: Sanjeevi
authors.forename: Robert M
authors.initials: RM
authors.lastname: Lowe
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Schaefer
authors.forename: Marjan
authors.initials: M
authors.lastname: Zarghami
authors.forename: Heather L
authors.initials: HL
authors.lastname: Day
authors.forename: Mona
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
authors.forename: Marta
authors.initials: M
authors.lastname: Janer-Villanueva
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Göran
authors.initials: G
authors.lastname: Sundkvist
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Norman
authors.initials: N
authors.lastname: Breslow
authors.forename: Gisela
authors.initials: G
authors.lastname: Dahlquist
authors.forename: Göran
authors.initials: G
authors.lastname: Blohmé
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D017678:Sex Distribution
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen