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

7 Scopus citations

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

Keywords

  • JIA
  • MHC
  • TAP
  • TDT

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Fingerprint Dive into the research topics of 'HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: More complexity within the MHC'. Together they form a unique fingerprint.

  • Cite this

    Runstadler, J. A., Säilä, H., Savolainen, A., Leirisalo-Repo, M., Aho, K., Tuomilehto-Wolf, E., Tuomilehto, J., & Seldin, M. F. (2004). HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: More complexity within the MHC. Genes and Immunity, 5(7), 562-571. https://doi.org/10.1038/sj.gene.6364129