Source:http://linkedlifedata.com/resource/pubmed/id/19898480
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2009-11-25
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pubmed:abstractText |
Gene-environment associations are important in rheumatoid arthritis (RA) susceptibility, with an association existing between smoking, HLA- DRB1 'shared epitope' alleles, PTPN22 and antibodies to cyclic citrullinated peptides (CCP). Here, we test the hypothesis that a subset of the anti-CCP response, with specific autoimmunity to citrullinated alpha-enolase, accounts for an important portion of these associations. In 1,497 individuals from three RA cohorts, antibodies to the immunodominant citrullinated alpha-enolase CEP-1 epitope were detected in 43-63% of the anti-CCP-positive individuals, and this subset was preferentially linked to HLA-DRB1*04. In a case-control analysis of 1,000 affected individuals and 872 controls, the combined effect of shared epitope, PTPN22 and smoking showed the strongest association with the anti-CEP-1-positive subset (odds ratio (OR) of 37, compared to an OR of 2 for the corresponding anti-CEP-1-negative, anti-CCP-positive subset). We conclude that citrullinated alpha-enolase is a specific citrullinated autoantigen that links smoking to genetic risk factors in the development of RA.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1546-1718
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pubmed:author |
pubmed-author:AlfredssonLarsL,
pubmed-author:CharlesPeterP,
pubmed-author:DingBoB,
pubmed-author:FisherBenjamin ABA,
pubmed-author:KällbergHenrikH,
pubmed-author:KlareskogLarsL,
pubmed-author:LundbergKarinK,
pubmed-author:MahdiHibaH,
pubmed-author:MalmströmVivianneV,
pubmed-author:PadyukovLeonidL,
pubmed-author:PlantDarrenD,
pubmed-author:RönnelidJohanJ,
pubmed-author:SymmonsDeborah P MDP,
pubmed-author:VenablesPatrick JPJ
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pubmed:issnType |
Electronic
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1319-24
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pubmed:dateRevised |
2010-10-4
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pubmed:meshHeading |
pubmed-meshheading:19898480-Arthritis, Rheumatoid,
pubmed-meshheading:19898480-Autoantibodies,
pubmed-meshheading:19898480-Autoimmunity,
pubmed-meshheading:19898480-Case-Control Studies,
pubmed-meshheading:19898480-Citrulline,
pubmed-meshheading:19898480-Genetic Predisposition to Disease,
pubmed-meshheading:19898480-Genotype,
pubmed-meshheading:19898480-Humans,
pubmed-meshheading:19898480-Phosphopyruvate Hydratase,
pubmed-meshheading:19898480-Smoking
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pubmed:year |
2009
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pubmed:articleTitle |
Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis.
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pubmed:affiliation |
Rheumatology Unit, Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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