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http://purl.uniprot.org/citations/19116923http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19116923http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The HLA-DRB1 locus within the major histocompatibility complex (MHC) at 6p21.3 has been identified as a susceptibility gene for rheumatoid arthritis (RA); however, there is increasing evidence of additional susceptibility genes in the MHC region. The aim of this study was to estimate their number and location.

Methods

A case-control study was performed involving 977 control subjects and 855 RA patients. The HLA-DRB1 locus was genotyped together with 2,360 single-nucleotide polymorphisms in the MHC region. Logistic regression was used to detect DRB1-independent effects.

Results

After adjusting for the effect of HLA-DRB1, 18 markers in 14 genes were strongly associated with RA (P<10(-4)). Multivariate logistic regression analysis of these markers and DRB1 led to a model containing DRB1 plus the following 3 markers: rs4678, a nonsynonymous change in the VARS2L locus, approximately 1.7 Mb telomeric of DRB1; rs2442728, upstream of HLA-B, approximately 1.2 Mb telomeric of DRB1; and rs17499655, located in the 5'-untranslated region of DQA2, only 0.1 Mb centromeric of DRB1. In-depth investigation of the DQA2 association, however, suggested that it arose through cryptic linkage disequilibrium with an allele of DRB1. Two non-shared epitope alleles were also strongly associated with RA (P<10(-4)): *0301 with anti-cyclic citrullinated peptide-negative RA and *0701 independently of autoantibody status.

Conclusion

These results confirm the polygenic contribution of the MHC to RA and implicate 2 additional non-DRB1 susceptibility loci. The role of the HLA-DQ locus in RA has been a subject of controversy, but in our data, it appears to be spurious."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.org/dc/terms/identifier"doi:10.1002/art.24138"xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Dickson M.C."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Vignal C."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Montgomery D.S."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Wilson A.G."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Balding D.J."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Bansal A.T."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/author"Binks M.H."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/pages"53-62"xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/title"Genetic association of the major histocompatibility complex with rheumatoid arthritis implicates two non-DRB1 loci."xsd:string
http://purl.uniprot.org/citations/19116923http://purl.uniprot.org/core/volume"60"xsd:string
http://purl.uniprot.org/citations/19116923http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19116923
http://purl.uniprot.org/citations/19116923http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19116923
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