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HLA associations in type 1 diabetes among patients not carrying high-risk DR3-DQ2 or DR4-DQ8 haplotypes

Undlien, Dag E. ; Kockum, I. ; Rønningen, K. S. ; Lowe, R. ; Saanjeevi, C. B. ; Graham, J. ; Lie, B. A. ; Akselsen, H. E. ; Lernmark, Å LU orcid and Thorsby, E. (1999) In Tissue Antigens 54(6). p.543-551
Abstract

Type 1 diabetes is a complex disease where numerous genes are involved in the pathogenesis. Genes that account for approximately 50% of the familial clustering of the disease are located within or in the vicinity of the HLA complex on chromosome 6. Some DRB1, DQA1 and DQB1 genes are known to be involved, in addition to as yet unidentified HLA-linked genes. The DR4-DQ8 and DR3-DQ2 haplotypes are known to confer high risk for developing the disease, particularly when occurring together. Approximately 10% of patients, however, do not carry any of these high-risk HLA class II haplotypes. We have performed genotyping of DRB1, DQA1 and DQB1 alleles in non-DR3-DQ2/non-DR4-DQ8 patients and controls from Sweden and Norway to test if any HLA... (More)

Type 1 diabetes is a complex disease where numerous genes are involved in the pathogenesis. Genes that account for approximately 50% of the familial clustering of the disease are located within or in the vicinity of the HLA complex on chromosome 6. Some DRB1, DQA1 and DQB1 genes are known to be involved, in addition to as yet unidentified HLA-linked genes. The DR4-DQ8 and DR3-DQ2 haplotypes are known to confer high risk for developing the disease, particularly when occurring together. Approximately 10% of patients, however, do not carry any of these high-risk HLA class II haplotypes. We have performed genotyping of DRB1, DQA1 and DQB1 alleles in non-DR3-DQ2/non-DR4-DQ8 patients and controls from Sweden and Norway to test if any HLA associations were observed in these patients. Our results clearly demonstrate several statistically significant differences in the frequency of HLA haplotypes between patients and controls. Case-control analysis including the relative predispositional effect test, and transmission disequilibrium test (TDT) analysis in Nonwegian type 1 diabetes families revealed that the DQA1*03-DQB1*0301, DQA1*0401-DQB1*0402, DQA1*0101-DQB1*0501, DQA1*03-DQB1*0303 and DQA1*0102-DQB1*0604 haplotypes may also confer risk. Our analyses also supported independent risks of certain DRB1 alleles. The study clearly demonstrates that HLA associations in type 1 diabetes extends far beyond the well-known associations with the DR4-DQ8 and DR3-DQ2 haplotypes. Our data suggest that there is a hierarchy of HLA class II haplotypes conferring risk to develop type 1 diabetes.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Disease susceptibility, Genotype, HLA class II antigens, Insulin-dependent diabetes mellitus, Transmission disequilibrium test (TDT)
in
Tissue Antigens
volume
54
issue
6
pages
543 - 551
publisher
Wiley-Blackwell
external identifiers
  • pmid:10674967
  • scopus:0033385183
ISSN
0001-2815
DOI
10.1034/j.1399-0039.1999.540602.x
language
English
LU publication?
no
id
cce5b812-e0d0-4807-8f5b-156389450f2f
date added to LUP
2019-06-30 23:25:44
date last changed
2024-03-13 08:11:57
@article{cce5b812-e0d0-4807-8f5b-156389450f2f,
  abstract     = {{<p>Type 1 diabetes is a complex disease where numerous genes are involved in the pathogenesis. Genes that account for approximately 50% of the familial clustering of the disease are located within or in the vicinity of the HLA complex on chromosome 6. Some DRB1, DQA1 and DQB1 genes are known to be involved, in addition to as yet unidentified HLA-linked genes. The DR4-DQ8 and DR3-DQ2 haplotypes are known to confer high risk for developing the disease, particularly when occurring together. Approximately 10% of patients, however, do not carry any of these high-risk HLA class II haplotypes. We have performed genotyping of DRB1, DQA1 and DQB1 alleles in non-DR3-DQ2/non-DR4-DQ8 patients and controls from Sweden and Norway to test if any HLA associations were observed in these patients. Our results clearly demonstrate several statistically significant differences in the frequency of HLA haplotypes between patients and controls. Case-control analysis including the relative predispositional effect test, and transmission disequilibrium test (TDT) analysis in Nonwegian type 1 diabetes families revealed that the DQA1*03-DQB1*0301, DQA1*0401-DQB1*0402, DQA1*0101-DQB1*0501, DQA1*03-DQB1*0303 and DQA1*0102-DQB1*0604 haplotypes may also confer risk. Our analyses also supported independent risks of certain DRB1 alleles. The study clearly demonstrates that HLA associations in type 1 diabetes extends far beyond the well-known associations with the DR4-DQ8 and DR3-DQ2 haplotypes. Our data suggest that there is a hierarchy of HLA class II haplotypes conferring risk to develop type 1 diabetes.</p>}},
  author       = {{Undlien, Dag E. and Kockum, I. and Rønningen, K. S. and Lowe, R. and Saanjeevi, C. B. and Graham, J. and Lie, B. A. and Akselsen, H. E. and Lernmark, Å and Thorsby, E.}},
  issn         = {{0001-2815}},
  keywords     = {{Disease susceptibility; Genotype; HLA class II antigens; Insulin-dependent diabetes mellitus; Transmission disequilibrium test (TDT)}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{6}},
  pages        = {{543--551}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Tissue Antigens}},
  title        = {{HLA associations in type 1 diabetes among patients not carrying high-risk DR3-DQ2 or DR4-DQ8 haplotypes}},
  url          = {{http://dx.doi.org/10.1034/j.1399-0039.1999.540602.x}},
  doi          = {{10.1034/j.1399-0039.1999.540602.x}},
  volume       = {{54}},
  year         = {{1999}},
}