Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.
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.
Graham
Jinko
J
Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, Canada.
Hagopian
William A
WA
Kockum
Ingrid
I
Li
Lou Sheng
LS
Sanjeevi
Carani B
CB
Lowe
Robert M
RM
Schaefer
Jonathan B
JB
Zarghami
Marjan
M
Day
Heather L
HL
Landin-Olsson
Mona
M
Palmer
Jerry P
JP
Janer-Villanueva
Marta
M
Hood
Leroy
L
Sundkvist
Göran
G
Lernmark
Ake
A
Breslow
Norman
N
Dahlquist
Gisela
G
Blohmé
Göran
G
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
D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen