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 ( approximately 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.

• Authors: J A Runstadler, H Säilä, A Savolainen, M Leirisalo-Repo, K Aho, E Tuomilehto-Wolf, J Tuomilehto, M F Seldin
• Journal: Genes and immunity (Genes Immun) Vol. 5 Issue 7 Pg. 562-71 (Nov 2004) ISSN: 1466-4879 [Print] England
• PMID: 15343265 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP Binding Cassette Transporter, Subfamily B, Member 3
• ATP-Binding Cassette Transporters
• HLA-DP Antigens
• HLA-DP beta-Chains
• HLA-DPB1 antigen
• HLA-DR Antigens
• HLA-DRB1 Chains
• TAP1 protein, human
• TAP2 protein, human

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP Binding Cassette Transporter, Subfamily B, Member 3
• ATP-Binding Cassette Transporters (genetics)
• Aged
• Arthritis, Juvenile (genetics)
• Case-Control Studies
• Chi-Square Distribution
• Child
• Child, Preschool
• Confidence Intervals
• Female
• Finland
• HLA-DP Antigens (genetics)
• HLA-DP beta-Chains
• HLA-DR Antigens (genetics)
• HLA-DRB1 Chains
• Haplotypes (genetics)
• Humans
• Major Histocompatibility Complex (genetics)
• Male
• Odds Ratio