HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC
Copyright policy )HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC
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.
- University of California, Davis United States
- Helsinki University Hospital Finland
- University of Helsinki Finland
Male, HLA-DP Antigens, Chi-Square Distribution, HLA-DR Antigens, Arthritis, Juvenile, Major Histocompatibility Complex, Haplotypes, ATP Binding Cassette Transporter, Subfamily B, Member 3, Case-Control Studies, Child, Preschool, Confidence Intervals, Humans, ATP-Binding Cassette Transporters, Female, ATP Binding Cassette Transporter, Subfamily B, Member 2, Child, Finland, HLA-DP beta-Chains, Aged, HLA-DRB1 Chains
Male, HLA-DP Antigens, Chi-Square Distribution, HLA-DR Antigens, Arthritis, Juvenile, Major Histocompatibility Complex, Haplotypes, ATP Binding Cassette Transporter, Subfamily B, Member 3, Case-Control Studies, Child, Preschool, Confidence Intervals, Humans, ATP-Binding Cassette Transporters, Female, ATP Binding Cassette Transporter, Subfamily B, Member 2, Child, Finland, HLA-DP beta-Chains, Aged, HLA-DRB1 Chains
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