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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-09-02

AUTHORS

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

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. More... »

PAGES

562-571

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gene.6364129

DOI

http://dx.doi.org/10.1038/sj.gene.6364129

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018300558

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15343265


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78 disequilibrium test (TDT) methods
79 effect
80 elderly Finnish control individuals
81 etiological differences
82 evidence
83 extended haplotypes
84 family
85 functional SNPs
86 functional etiological differences
87 genetic susceptibility
88 haplotypes
89 haplotypic analysis
90 idiopathic arthritis
91 implications
92 independent effects
93 individuals
94 interaction
95 juvenile idiopathic arthritis
96 loci
97 marker analysis
98 method
99 more complexity
100 negative JIA subgroup
101 negative disease
102 nuclear families
103 observations
104 patients
105 polyarticular JIA patients
106 polyarticular RF negative JIA subgroup
107 polyarticular RF negative disease
108 region
109 sequence
110 single marker analysis
111 strong effect
112 study
113 subgroups
114 subset
115 susceptibility
116 test method
117 transmission disequilibrium test (TDT) methods
118 variety
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