Document Detail

Association of the TRAF1/C5 locus with increased mortality, particularly from malignancy or sepsis, in patients with rheumatoid arthritis.
MedLine Citation:
PMID:  19116907     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Recent genome-wide association studies have identified TRAF1/C5 as a rheumatoid arthritis (RA) susceptibility locus. Tumor necrosis factor receptor-associated factor 1 (TRAF1) has been implicated in the regulation of antiapoptotic pathways, whereas C5 has a well-established role in defense against infection. The purpose of this study was to examine the association of the TRAF1/C5 locus with death in patients with RA. METHODS: Genomic DNA samples were collected from a prospective cohort of 400 RA patients. TRAF1/C5 rs3761847 was identified using real-time polymerase chain reaction and melting curve analyses. The association of TRAF1/C5 rs3761847 alleles with the risk of death was assessed using Cox proportional hazards regression analyses. RESULTS: TRAF1/C5 rs3761847 GG homozygote status was associated with an increased risk of death (hazard ratio 3.96 [95% confidence interval 1.24-12.6], P=0.020) as compared with AA homozygote status. The excess mortality was attributed to deaths due to malignancies and sepsis but not cardiovascular disease (CVD). This polymorphism was one of the strongest predictors of death in RA (for TRAF1/C5 GG versus AA, hazard ratio 3.85 [95% confidence interval 1.18-12.59], P=0.026) alongside the erythrocyte sedimentation rate, triglyceride level, prednisolone use, and age. CONCLUSION: The risk of death in RA is increased in TRAF1/C5 rs3761847 GG homozygotes and appears to be independent of RA activity and severity as well as comorbidities relevant to CVD. If this finding is replicated in future studies, TRAF1/C5 genotyping could identify patients at increased risk of death, particularly death due to malignancy or sepsis.
Vasileios F Panoulas; Jacqueline P Smith; Peter Nightingale; George D Kitas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  60     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-03-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-46     Citation Subset:  AIM; IM    
Dudley Group of Hospitals National Health Service Trust, Dudley, UK.
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MeSH Terms
Arthritis, Rheumatoid / genetics,  mortality*
Cause of Death
Cohort Studies
Complement C5 / genetics*
Gene Frequency
Middle Aged
Multivariate Analysis
Neoplasms / genetics,  mortality*
Polymorphism, Single Nucleotide
Proportional Hazards Models
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Sepsis / genetics,  mortality*
TNF Receptor-Associated Factor 1 / genetics*
Reg. No./Substance:
0/Complement C5; 0/TNF Receptor-Associated Factor 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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