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Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.

Graham, J ; Hagopian, WA ; Kockum, I ; Li, LS ; Sanjeevi, CB ; Lowe, RM ; Schaefer, JB ; Zarghami, M ; Day, HL and Landin-Olsson, Mona LU , et al. (2002) In Diabetes 51(5). p.1346-1355
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
51
issue
5
pages
1346 - 1355
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000175492400005
  • pmid:11978629
  • scopus:0036319041
ISSN
1939-327X
DOI
10.2337/diabetes.51.5.1346
language
English
LU publication?
yes
id
c861f531-f055-4415-ac63-22ecb7342429 (old id 119287)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11978629&dopt=Abstract
date added to LUP
2016-04-01 16:23:37
date last changed
2024-01-11 07:10:48
@article{c861f531-f055-4415-ac63-22ecb7342429,
  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 &lt; 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 &lt; 0.0001) and with DQ2 (P &lt; 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P &lt; 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.}},
  author       = {{Graham, J and Hagopian, WA and Kockum, I and Li, LS and Sanjeevi, CB and Lowe, RM and Schaefer, JB and Zarghami, M and Day, HL and Landin-Olsson, Mona and Palmer, JP and Janer-Villanueva, M and Hood, L and Sundkvist, G and Lernmark, Åke and Breslow, N and Dahlquist, G and Blohme, G}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1346--1355}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.}},
  url          = {{http://dx.doi.org/10.2337/diabetes.51.5.1346}},
  doi          = {{10.2337/diabetes.51.5.1346}},
  volume       = {{51}},
  year         = {{2002}},
}