Navigation Links
The HLA-DRB1 gene and premature death in rheumatoid arthritis
Date:1/30/2008

People with rheumatoid arthritis (RA), an inflammatory autoimmune disease, tend to die younger and, largely from cardiovascular disease (CVD). One explanation for this increasingly recognized fact is that inflammation promotes atherosclerosis. A marker of inflammation, elevation of the C-reactive protein (CRP) level has been shown to predict CVD in the general population. However, other highly inflammatory diseasesCrohns, for exampledo not carry the same high risk of premature death from heart disease.

To identify other possible suspects, researchers in the United Kingdom investigated whether genetic variants linked to the likelihood of developing RA might also make patients more likely to die from CVD. Led by Dr. Tracey M. Farragher at the University of Manchester and funded by the Arthritis Research Campaign (arc), the study focused on two genesHLA-DRB1and PTPN22and their interactions with known RA risk factors. The evidence, presented in the February 2008 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), implicates HLA-DRB1 genotypes, already associated with RA susceptibility and severity, as a predictor of premature death from CVD for inflammatory arthritis patients. For RA patients in particular, having the shared epitope (SE)a group of HLA-DRB1 alleles with kindred amino acid traitsplus anti-cyclic citrullinated peptide (anti-CCP) antibodies and current smoking is an especially deadly combination.

The study focused on 1,022 patients with inflammatory polyarthritis (IP) recruited from a primary-care-based register of adults. The subjects were all white and nearly 65 percent female, with a mean age of 54 at the onset of symptoms. Starting anywhere between 1989 and 1994, data on file for each participant included the results of blood tests for rheumatoid factor (RF), elevation of the C-reactive protein (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 of smoking for anyone with a genetic predisposition for arthritis.


'/>"/>

Contact: Amy Molnar
amolnar@wiley.com
Wiley-Blackwell
Source:Eurekalert

Related medicine news :

1. More babies born prematurely, new report shows
2. $4 million nursing grant focuses on at-risk premature infants
3. Repeat steroids to premature infants linked to cerebral palsy
4. Amid Improving Life Expectancy Rates, Risk of Premature Death is Still Significant for Americans, New Study Shows
5. Using the safety belt in the rear seats of the car reduces death risk by almost a half
6. Heart and stroke death rates steadily decline; risks still too high
7. Daily exercise dramatically lowers mens death rates
8. U.S. Deaths Down From Heart Disease, Stroke
9. One-third of stunting and a quarter of deaths among under 3s in poor countries could be prevented
10. Study finds significant differences in protocols hospitals use to determine brain death
11. Malnutrition Responsible for a Third of Child Deaths Worldwide
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/17/2017)... ... August 17, 2017 , ... Aeroflow Healthcare today ... recognizing America’s fastest growing private companies. Inc. magazine ranked Aeroflow Healthcare #2450 on ... , The Inc. 5000 represents the most comprehensive study of American ...
(Date:8/17/2017)... ... August 17, 2017 , ... SeQuel Response announced ... multichannel growth agency among the fastest-growing private companies in the U.S., putting it in ... companies that have applied to the Inc. 5000 over the years, only ...
(Date:8/17/2017)... ... August 17, 2017 , ... With the introduction of new ... a number of changes to the smartwatch market. As of June 2017, nearly nine ... from the six months prior. Additionally, according to latest WEAR Report Industry Overview and ...
(Date:8/17/2017)... ... August 17, 2017 , ... Inc. Magazine Unveils 36th Annual List ... with Three-Year Sales Growth of 3,004.8% , NEW YORK, August 16, 2017 – Inc. ... most prestigious ranking of the nation's fastest-growing private companies. The list represents a unique ...
(Date:8/17/2017)... ... August 17, 2017 , ... Advice Media, the industry leader in digital marketing for medical practices, ... and has been included in the Inc. 5000 for the second time in two years. ... in the Inc. 5000 rankings for the second year in a row. It’s extremely difficult ...
Breaking Medicine News(10 mins):
(Date:8/2/2017)... Aug. 2, 2017  Life Flight Network and PeaceHealth Oregon ... improves patient care and operational efficiency for patients at hospitals ... , Cottage Grove , and ... PeaceHealth and Life Flight Network work collaboratively to move patients ... or when a time sensitive emergency exists. ...
(Date:8/1/2017)... , Aug. 1, 2017   CerSci Therapeutics , ... Dallas, Texas , has received notice from the ... Institutes of Health (NIH) that it has been awarded ... totaling over $650,000 in 2017 with an additional $1,000,000 ... Investigational New Drug application of their lead non-opioid drug ...
(Date:7/31/2017)... Three Tru-D SmartUVC robots have arrived at Brian ... . Tru-D, short for "Total Room Ultraviolet Disinfection," is a 5-foot-5 germ-killing ... services (ES) professional cleans the area with traditional cleaning protocols. ... Tru-D fights germs at Army ... "Although the BAACH has a very low infection ...
Breaking Medicine Technology: