A study suggests that the risk for death associated with rheumatoid arthritis (RA) is increased in patients who are homozygous carriers of the G allele for the tumor necrosis factor (TNF) receptor-associated factor 1/complement 5 (TRAF-1/C5) rs3761847 genotype.
The mortality risk appears to be independent of RA activity and severity as well as comorbidities relevant to cardiovascular disease (CVD), the research suggests.
George Kitas (Russells Hall Hospital, Dudley, West Midlands, UK) and colleagues call for further studies designed to uncover potential underlying mechanisms for this association.
It is well established that any genetic variations in the TRAF1 region may affect regulatory pathways of the cell cycle and lead to oncogenesis as a result of suppression of TNF-α or T-cell receptor-mediated apoptosis. Similarly, C5 plays an important role in the defense system against infection.
In their study, the researchers collected genomic DNA samples from a prospective cohort of 400 RA patients with mean age 61.6 years, of whom 73% were women. TRAF1/C5 rs3761847 was identified and its association with the risk for death was assessed. The mean follow-up time for the study was 31.4 months.
Kitas et al found that TRAF1/C5 rs3761847 GG homozygote status was associated with an increased risk for death compared with AA homozygote status (hazard ratio
=3.96). Furthermore, G allele carriers were more often anti-cyclic citrullinated peptide positive compared with AA homozygotes (74.75% vs 70.75% vs 57.5% for GG, GA, and AA, respectively).
Following a multivariable analysis, the authors note that erythrocyte sedimentation rate, triglyceride levels, use of steroids, and age were also predictors for death (HR=1.02, 1.64, 3.33, and 1.05, respectively).
Furthermore, the researchers found no significant differences observed in deaths from CVD across genotype groups. Conversely, they uncovered significant differences in death rates due to malignancy and sepsis among GG homozygotes compared with AA and AG carriers (5.1% vs 0% and 1.0%, respectively).
“If this finding is replicated in future studies, TRAF1/C5 genotyping could identify patients at increased risk for death, particularly death due to malignancy or sepsis,” the team concludes in the journal Arthritis & Rheumatism.
I haven't read it, Lynn.. but you do better at dissecting these abstracts than I can ever hope to... but as far as co-morbidy of cardiovascular disease.. that's genetic too yet independent? of the gene that gives us the AI diseases? ..... so the father w/ Gout and RA, will pass on his need to have a quint by-pass to me when I reach my late 60's?????
[QUOTE=babs10]
I haven't read it, Lynn.. but you do better at dissecting these abstracts than I can ever hope to... but as far as co-morbidy of cardiovascular disease.. that's genetic too yet independent? of the gene that gives us the AI diseases? ..... so the father w/ Gout and RA, will pass on his need to have a quint by-pass to me when I reach my late 60's?????
[/QUOTE]