HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: More complexity within the MHC

J. A. Runstadler, H. Säilä, A. Savolainen, M. Leirisalo-Repo, K. Aho, E. Tuomilehto-Wolf, J. Tuomilehto, Michael F Seldin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci (∼200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1*030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1*030101 and DRB1*08 and *11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1*08 and *11 (P< 0.000003) and DPB1* 030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

Original languageEnglish (US)
Pages (from-to)562-571
Number of pages10
JournalGenes and Immunity
Volume5
Issue number7
DOIs
StatePublished - Nov 2004

Fingerprint

HLA-DRB1 Chains
Juvenile Arthritis
Haplotypes
Alleles
Genetic Predisposition to Disease
Nuclear Family
Single Nucleotide Polymorphism
HLA-DPB1 antigen
DNA

Keywords

  • JIA
  • MHC
  • TAP
  • TDT

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis : More complexity within the MHC. / Runstadler, J. A.; Säilä, H.; Savolainen, A.; Leirisalo-Repo, M.; Aho, K.; Tuomilehto-Wolf, E.; Tuomilehto, J.; Seldin, Michael F.

In: Genes and Immunity, Vol. 5, No. 7, 11.2004, p. 562-571.

Research output: Contribution to journalArticle

Runstadler, JA, Säilä, H, Savolainen, A, Leirisalo-Repo, M, Aho, K, Tuomilehto-Wolf, E, Tuomilehto, J & Seldin, MF 2004, 'HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: More complexity within the MHC', Genes and Immunity, vol. 5, no. 7, pp. 562-571. https://doi.org/10.1038/sj.gene.6364129
Runstadler JA, Säilä H, Savolainen A, Leirisalo-Repo M, Aho K, Tuomilehto-Wolf E et al. HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: More complexity within the MHC. Genes and Immunity. 2004 Nov;5(7):562-571. https://doi.org/10.1038/sj.gene.6364129
Runstadler, J. A. ; Säilä, H. ; Savolainen, A. ; Leirisalo-Repo, M. ; Aho, K. ; Tuomilehto-Wolf, E. ; Tuomilehto, J. ; Seldin, Michael F. / HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis : More complexity within the MHC. In: Genes and Immunity. 2004 ; Vol. 5, No. 7. pp. 562-571.
@article{44ec1c1341ed4987a3c7a4747d5bfac9,
title = "HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: More complexity within the MHC",
abstract = "This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci (∼200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1*030101 allele for JIA (OR 2.3, 95{\%} CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1*030101 and DRB1*08 and *11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1*08 and *11 (P< 0.000003) and DPB1* 030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.",
keywords = "JIA, MHC, TAP, TDT",
author = "Runstadler, {J. A.} and H. S{\"a}il{\"a} and A. Savolainen and M. Leirisalo-Repo and K. Aho and E. Tuomilehto-Wolf and J. Tuomilehto and Seldin, {Michael F}",
year = "2004",
month = "11",
doi = "10.1038/sj.gene.6364129",
language = "English (US)",
volume = "5",
pages = "562--571",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis

T2 - More complexity within the MHC

AU - Runstadler, J. A.

AU - Säilä, H.

AU - Savolainen, A.

AU - Leirisalo-Repo, M.

AU - Aho, K.

AU - Tuomilehto-Wolf, E.

AU - Tuomilehto, J.

AU - Seldin, Michael F

PY - 2004/11

Y1 - 2004/11

N2 - This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci (∼200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1*030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1*030101 and DRB1*08 and *11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1*08 and *11 (P< 0.000003) and DPB1* 030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

AB - This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci (∼200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1*030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1*030101 and DRB1*08 and *11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1*08 and *11 (P< 0.000003) and DPB1* 030101 (P=0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

KW - JIA

KW - MHC

KW - TAP

KW - TDT

UR - http://www.scopus.com/inward/record.url?scp=8844245608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8844245608&partnerID=8YFLogxK

U2 - 10.1038/sj.gene.6364129

DO - 10.1038/sj.gene.6364129

M3 - Article

C2 - 15343265

AN - SCOPUS:8844245608

VL - 5

SP - 562

EP - 571

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 7

ER -