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Non-HLA type 1 diabetes genes modulate disease risk together with HLA-DQ and islet autoantibodies.

Maziarz, M; Hagopian, W; Palmer, J P; Sanjeevi, C B; Kockum, I; Breslow, N and Lernmark, Åke LU (2015) In Genes and Immunity 16(8). p.541-551
Abstract
The possible interrelations between human leukocyte antigen (HLA)-DQ, non-HLA single-nucleotide polymorphisms (SNPs) and islet autoantibodies were investigated at clinical onset in 1-34-year-old type 1 diabetes (T1D) patients (n=305) and controls (n=203). Among the non-HLA SNPs reported by the Type 1 Diabetes Genetics Consortium, 24% were supported in this Swedish replication set including that the increased risk of minor PTPN22 allele and high-risk HLA was modified by GAD65 autoantibodies. The association between T1D and the minor AA+AC genotype in ERBB3 gene was stronger among IA-2 autoantibody-positive patients (comparison P=0.047). The association between T1D and the common insulin (AA) genotype was stronger among insulin autoantibody... (More)
The possible interrelations between human leukocyte antigen (HLA)-DQ, non-HLA single-nucleotide polymorphisms (SNPs) and islet autoantibodies were investigated at clinical onset in 1-34-year-old type 1 diabetes (T1D) patients (n=305) and controls (n=203). Among the non-HLA SNPs reported by the Type 1 Diabetes Genetics Consortium, 24% were supported in this Swedish replication set including that the increased risk of minor PTPN22 allele and high-risk HLA was modified by GAD65 autoantibodies. The association between T1D and the minor AA+AC genotype in ERBB3 gene was stronger among IA-2 autoantibody-positive patients (comparison P=0.047). The association between T1D and the common insulin (AA) genotype was stronger among insulin autoantibody (IAA)-positive patients (comparison P=0.008). In contrast, the association between T1D and unidentified 26471 gene was stronger among IAA-negative (comparison P=0.049) and IA-2 autoantibody-negative (comparison P=0.052) patients. Finally, the association between IL2RA and T1D was stronger among IAA-positive than among IAA-negative patients (comparison P=0.028). These results suggest that the increased risk of T1D by non-HLA genes is often modified by both islet autoantibodies and HLA-DQ. The interactions between non-HLA genes, islet autoantibodies and HLA-DQ should be taken into account in T1D prediction studies as well as in prevention trials aimed at inducing immunological tolerance to islet autoantigens.Genes and Immunity advance online publication, 29 October 2015; doi:10.1038/gene.2015.43. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes and Immunity
volume
16
issue
8
pages
541 - 551
publisher
Nature Publishing Group
external identifiers
  • pmid:26513234
  • wos:000365976200006
  • scopus:84949107978
ISSN
1476-5470
DOI
10.1038/gene.2015.43
language
English
LU publication?
yes
id
756b605c-2545-43e7-ab6e-4476e91800a7 (old id 8147939)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26513234?dopt=Abstract
date added to LUP
2015-11-04 18:51:04
date last changed
2017-07-23 03:09:15
@article{756b605c-2545-43e7-ab6e-4476e91800a7,
  abstract     = {The possible interrelations between human leukocyte antigen (HLA)-DQ, non-HLA single-nucleotide polymorphisms (SNPs) and islet autoantibodies were investigated at clinical onset in 1-34-year-old type 1 diabetes (T1D) patients (n=305) and controls (n=203). Among the non-HLA SNPs reported by the Type 1 Diabetes Genetics Consortium, 24% were supported in this Swedish replication set including that the increased risk of minor PTPN22 allele and high-risk HLA was modified by GAD65 autoantibodies. The association between T1D and the minor AA+AC genotype in ERBB3 gene was stronger among IA-2 autoantibody-positive patients (comparison P=0.047). The association between T1D and the common insulin (AA) genotype was stronger among insulin autoantibody (IAA)-positive patients (comparison P=0.008). In contrast, the association between T1D and unidentified 26471 gene was stronger among IAA-negative (comparison P=0.049) and IA-2 autoantibody-negative (comparison P=0.052) patients. Finally, the association between IL2RA and T1D was stronger among IAA-positive than among IAA-negative patients (comparison P=0.028). These results suggest that the increased risk of T1D by non-HLA genes is often modified by both islet autoantibodies and HLA-DQ. The interactions between non-HLA genes, islet autoantibodies and HLA-DQ should be taken into account in T1D prediction studies as well as in prevention trials aimed at inducing immunological tolerance to islet autoantigens.Genes and Immunity advance online publication, 29 October 2015; doi:10.1038/gene.2015.43.},
  author       = {Maziarz, M and Hagopian, W and Palmer, J P and Sanjeevi, C B and Kockum, I and Breslow, N and Lernmark, Åke},
  issn         = {1476-5470},
  language     = {eng},
  number       = {8},
  pages        = {541--551},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Non-HLA type 1 diabetes genes modulate disease risk together with HLA-DQ and islet autoantibodies.},
  url          = {http://dx.doi.org/10.1038/gene.2015.43},
  volume       = {16},
  year         = {2015},
}