ArticleGenes and immunity2011
Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population.
Article in Genes and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 5 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 5 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis.Annals of the rheumatic diseases · 2021Guideline
- Association betweenAging · 2021Pooled it
- Associations between CCL21 gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis.Rheumatology international · 2017Pooled it
- Association between susceptibility to rheumatoid arthritis and PADI4 polymorphisms: a meta-analysis.Clinical rheumatology · 2016Pooled it
- The PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis.Rheumatology international · 2013Pooled it
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- Exploration of potential novel drug targets for rheumatoid arthritis by plasma proteome screening.PLoS computational biology · 2025Article
- Targeting rheumatoid arthritis risk factors with phytochemicals: an anti-inflammatory perspective.Inflammopharmacology · 2025Review
- Disparities in rheumatoid arthritis outcomes for North American Indigenous populations.International journal of circumpolar health · 2023Review
- Genomics and inclusion of Indigenous peoples in high income countries.Human genetics · 2023Review
- Overview of Rheumatoid Arthritis and Scientific Understanding of the Disease.Mediterranean journal of rheumatology · 2023Review
- Single Nucleotide Polymorphisms Associated with Rheumatoid Arthritis in Saudi Patients.Journal of clinical medicine · 2023Article
- Novel functional polymorphism onSaudi journal of biological sciences · 2022Article
- The Association BetweenFrontiers in medicine · 2021Article
- Platelet-to-Lymphocyte Ratio as an Independent Factor Was Associated With the Severity of Ankylosing Spondylitis.Frontiers in immunology · 2021Article
- Associations ofCentral-European journal of immunology · 2019Article
- Systematic approach demonstrates enrichment of multiple interactions between non-Annals of the rheumatic diseases · 2018Article
- Whole blood microRNA expression pattern differentiates patients with rheumatoid arthritis, their seropositive first-degree relatives, and healthy unrelated control subjects.Arthritis research & therapy · 2017Article
- Associations of Smoking and Age With Inflammatory Joint Signs Among Unaffected First-Degree Relatives of Rheumatoid Arthritis Patients: Results From Studies of the Etiology of Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA.Rheumatology (Oxford, England) · 2016Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Most of the genetic risk for rheumatoid arthritis (RA) is conferred by 'shared epitope' (SE), encoding alleles of HLA-DRB1. Specific North American Native (NAN) populations have RA prevalence rates of 2-5%, representing some of the highest rates estimated worldwide. As many NAN populations also demonstrate a high background frequency of SE, we sought to determine whether other genetic factors contribute to disease risk in this predisposed population. RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL. Our findings indicate that SE is prevalent and represents a major genetic risk factor for RA in this population (82% cases versus 68% controls, odds ratio=2.2, 95% confidence interval 1.6-3.1, P<0.001). We also demonstrate that in the presence of SE, the minor allele of MMEL1-TNFRSF14 significantly reduces RA risk in a dominant manner, whereas TRAF1-C5 increases the risk. These findings point to the importance of non-HLA genes in determining RA risk in a population with a high frequency of disease predisposing HLA-DRB1 alleles.
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Registered trials
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