The HLA-DRB1 gene and premature death in rheumatoid...(CRP) and anti-CCP antibodies; evaluation...),Health

Date:1/30/2008

CRP), and anti-CCP antibodies; evaluations of joint pain and functional disability; smoking habits; and, when applicable, the cause and date of death. DNA samples were also available. 751 of the total patients met the American College of Rheumatology criteria for RA.

HLA-DRB1 and PTPN22 genotyping was performed on every patients DNA. Using Cox proportional hazards regression models, researchers assessed the association of each gene family with the risk of death from all causes and from cardiovascular disease. They also examined the interactions between SE presence, anti-CCP status, and smoking history, adjusted by patient sex and age at symptom onset.

In the years between the registers inception and the studys completion, 242 (24 percent) of the patients died. CVD was named as the cause of death for 76 (31.4 percent) of the deceased. Based on the researchers analyses, having two copies of the SE alleles increased the risk of death from all causes and from CVD. For individuals with the HLA-DRB1 combination, the risk of death from CVD was increased more than 3-fold. The fatal impact was independent of RF and CRP levels. It was aggravated, however, by the interaction of SE, anti-CCP antibodies, and smoking. Current smokers who carried 2 SE alleles and had anti-CCP antibodies had the highest risk of dying from all causes, as well as a substantially higher risk of dying early from CVD. In calculations focusing on RA patients only, this finding remained consistent. Researchers found no evidence of any association between the PTPN22 gene and the risk of death.

This study is the first to link the HLA-DRB1 genotype with premature death, particularly from cardiovascular disease, for those afflicted with any form of inflammatory arthritis, including RA. As Dr. Farragher stresses, the results raise the possibility of a targeted strategy to prevent CVD in these patients, while reinforcing the lethal danger
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Contact: Amy Molnar amolnar@wiley.com Wiley-Blackwell Source:Eurekalert

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