ArticleAnnals of the rheumatic diseases2007
Opposing effects of the D70 mutation and the shared epitope in HLA-DR4 on disease activity and certain disease phenotypes in rheumatoid arthritis.
Article in Annals of the rheumatic diseases, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The influence of polygenic risk scores on heritability of anti-CCP level in RA.Genes and immunity · 2014Pooled it
- Article
- Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Human Leukocyte Antigen-Disease Associations in Rheumatoid Arthritis.Rheumatic diseases clinics of North America · 2017Review
- A reciprocal HLA-Disease Association in Rheumatoid Arthritis and Pemphigus Vulgaris.Frontiers in bioscience (Landmark edition) · 2017Review
- Functional impact of a spectrum of interstitial lung abnormalities in rheumatoid arthritis.Chest · 2014Observational
- Associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis.The Journal of rheumatology · 2014Article
- Genetics and epigenetics of rheumatoid arthritis.Nature reviews. Rheumatology · 2013Review
- Article
- A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population.Genes and immunity · 2012Article
- Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and is prevalent in autoantibodies in rheumatoid arthritis.Arthritis and rheumatism · 2010Article
- A broad analysis of IL1 polymorphism and rheumatoid arthritis.Arthritis and rheumatism · 2008Article
- Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibody titer in adults with rheumatoid arthritis.Molecular medicine (Cambridge, Mass.)Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCertain sequences present in the hypervariable region of human leucocyte antigen (HLA)-DRB1 known as the shared epitope (SE) are hypothesised to increase the risk of rheumatoid arthritis (RA), whereas alleles encoding aspartic acid at position 70 (D70 alleles) may have a protective effect.
methodsPatient HLA-DRB1 serotypes were assessed and the genotypes encoding the SE motif or the putatively protective D70 motif identified in a large RA cohort. Logistic regression was used to analyse associations of genotype with presence of disease, comorbidities and disease severity, and association between genotype and change in disease activity over time.
resultsThe 689 patients enrolled had a mean (SD) age of 57.9 (13.7) years and mean (SD) disease duration of 15.3 (12.7) years. In a comparison with 482 ethnicity matched population-based controls, the D70 sequence exerted a strong protective effect (OR = 0.52, p<0.001) that remained significant when the SE at the same locus was accounted for (OR = 0.72, 95% CI 0.60 to 0.86, p<0.001). The SE assessed on all HLA-DRB1 serotypic backgrounds except DR1 was associated with RA susceptibility (additive OR = 2.43, p<0.001). Associations were found between SE and serum levels of rheumatoid factor (p<0.001, with correlation of 0.18) and anti-cyclic citrullinated peptide antibodies (p<0.001, with correlation of 0.25) but not with serum C-reactive protein.
conclusionThe D70 allele has a significant protective effect that is mitigated but still significant when the risk effect of the SE at the same locus is taken into account. The presence of the SE on DR4 is associated with greater RA susceptibility and certain disease-activity measures.
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