<i>TRAF1–C5</i>as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study

Plenge, Robert M.; Seielstad, Mark; Padyukov, Leonid; Lee, Annette T.; Remmers, Elaine F.; Ding, Bo; Liew, Anthony; Khalili, Houman; Chandrasekaran, Alamelu; Davies, Leela R.L.; Li, Wentian; Tan, Adrian; Bonnard, Carine; Ong, Rick Twee Hee; Thalamuthu, Anbupalam; Pettersson, Sven; Liu, Chunyu; Tian, Chao; Chen, Wei V.; Carulli, John P.; Beckman, Evan M.; Altshuler, David; Alfredsson, Lars; Criswell, Lindsey A.; Amos, Christopher I.; Seldin, Michael F.; Kastner, Daniel L.; Klareskog, Lars; Gregersen, Peter K.

doi:10.1056/nejmoa073491

Cited by 746 publications

(765 citation statements)

References 48 publications

Supporting

Mentioning

708

Contrasting

Unclassified

Order By: Relevance

“…[26][27][28] TRAF1-C5 was previously reported to be associated with RA in primarily Caucasian populations. 29 The OR for association with the minor allele of the rs3761847 SNP was reported at 1.32, which is comparable to an OR of 1.23 we report in the NAN population, using the same SNP. We further demonstrate that the OR is increased to 1.48 when analyzing SE positive cases and controls, and as with MMEL1-TNFRSF14, there is an indication of a significant interaction with SE.…”

Section: Discussionsupporting

confidence: 71%

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population

et al. 2011

View full text Add to dashboard Cite

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 ¼ 333) and controls (n ¼ 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 ¼ 2.2, 95% confidence interval 1.6-3.1, Po0.001). 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.

show abstract

Section: Discussionsupporting

confidence: 71%

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Neither RGMA, IL4R nor IL21R has been identified as the gene that is involved in autoimmune diseases in GWA scans. 7,11,14,31,51,52 The region that we report associated in the RGMA region has reasonable coverage of markers in these scans, although rs34925346 marker was not included in any of the scans, nor was stratification-based sex performed in all GWA scans. For IL21R, the poor marker coverage in GWA scans in the region we identified as associated with MS may explain why this gene has not associated with autoimmune diseases in GWA studies.…”

Section: Eae30mentioning

confidence: 92%

RGMA and IL21R show association with experimental inflammation and multiple sclerosis

et al. 2010

View full text Add to dashboard Cite

“…RA is caused by a combination of genetic susceptibility and environmental factors, including not only increased antibody levels of measles virus but also by vaccine strain [114]. A few case reports describe arthritis as a common complication of wild rubella virus in adults, but it occurs less often in children; that in several cases represents the first RA clinical manifestation [115].…”

Section: Mmr Vaccine and Rheumatoid Arthritismentioning

confidence: 99%

Vaccination and autoimmune diseases: is prevention of adverse health effects on the horizon?

et al. 2017

View full text Add to dashboard Cite

Autoimmune diseases, including multiple sclerosis and type 1 diabetes mellitus, affect about 5% of the worldwide population. In the last decade, reports have accumulated on various autoimmune disorders, such as idiopathic thrombocytopenia purpura, myopericarditis, primary ovarian failure, and systemic lupus erythematosus (SLE), following vaccination. In this review, we discuss the possible underlying mechanisms of autoimmune reactions following vaccinations and review cases of autoimmune diseases that have been correlated with vaccination. Molecular mimicry and bystander activation are reported as possible mechanisms by which vaccines can cause autoimmune reactions. The individuals who might be susceptible to develop these reactions could be especially not only those with previous post-vaccination phenomena and those with allergies but also in individuals who are prone to develop autoimmune diseases, such as those with a family history of autoimmunity or with known autoantibodies, and the genetic predisposed individuals.Further research is encouraged into the direct associations between vaccines and autoimmune conditions, and the biological mechanisms behind them.

show abstract

TRAF1–C5as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study

Cited by 746 publications

References 48 publications

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population

RGMA and IL21R show association with experimental inflammation and multiple sclerosis

Vaccination and autoimmune diseases: is prevention of adverse health effects on the horizon?

Contact Info

Product

Resources

About