Re: The impact of smoking and genes on rheumatoid arthritis

[Guest guest]

a, this is interesting and is true. January of 1995 I was in the

hospital for four days

with a blood clot in my left leg. The first thing my Dr. said was " when did

you

quit smoking. " I have never smoked a cigarette a day in my life. I also

have RA and

Raynauds Disease. Not only is RA painful but so is Raynauds if your hands

get cold.

When your fingers get cold they will turn colors to a blanch, purple, red,

then back to

blanch. It is very painful through the whole process. I didn't know until

recently that

Raynauds Disease is listed under Arthritis diseases.

Joyce from Texas

[ ] The impact of smoking and genes on rheumatoid

arthritis

The impact of smoking and genes on rheumatoid arthritis

Researchers offer new insight into specific autoimmune triggers among

smokers with shared epitope genes

Rheumatoid arthritis (RA) is one of the most common systemic

autoimmune diseases, and one of the least understood. Smoking is the

major known environmental risk factor for RA, though little is known

about the mechanisms involved. HLA-DR shared epitope (SE) genes are a

widely recognized genetic risk factor for RA, though little is known

about how these genes affect autoimmune reactions that lead to

chronic inflammation and progressive joint and organ damage.

To better understand the interactions between smoking and HLA-DR SE

genes in RA, a team of researchers in Sweden focused on the disease's

distinctive autoimmune hallmark: citrulline, an amino acid not

normally present in protein. While extremely rare in healthy

individuals and relatively rare in other inflammatory conditions,

citrulline-modified proteins are common in about two-thirds of RA

patients and may be an underlying factor in the development of the

disease. To investigate whether smoking and SE genes trigger immune

reactions to citrullinated proteins, the team conducted a case-

control study involving patients with recent-onset RA. The results,

featured in the January 2006 issue of Arthritis & Rheumatism (http://

www.interscience.wiley.com/journal/arthritis), suggest that smokers

with SE genes are more susceptible to anticitrulline antibody-

positive RA.

The study's 930 early RA patients, drawn from the Epidemiological

Investigation of Rheumatoid Arthritis Study Group, ranged in age from

18 to 70 years. 383 healthy controls, drawn from the blood bank of

northern Sweden, were matched for age, gender, and residential area.

All participants completed questionnaires about their past and

present smoking habits, as well as genotyping profiles. In addition,

bronchial fluid was obtained from a representative sample of RA

patients, including both current heavy smokers and lifelong non-

smokers, and tested with immunostaining for the presence of

citrullinated protein in cells.

Based on their series of experiments and comparisons, the researchers

found that a history of smoking increases the risk for RA, but only

for individuals who test positive for anticitrulline antibodies,

regardless of the presence of SE genes. Similarly, inheriting HLA-DR

SE genes in a single copy, as well as in double copies, increases the

risk for RA, but only for individuals who test positive for

anticitrulline antibodies, including individuals who have never

smoked. Yet, for individuals who test positive for anticitrulline

antibodies, the interaction of smoking and carrying 2 copies of the

SE gene dramatically increases the risk for developing RA--by 21 times.

" The remarkable gene-environment interaction observed in the case-

control study, together with the immunostaining for citrullinated

proteins, might now provide a clue to the molecular mechanisms of

importance for disease development in a subset of RA patients, " notes

team spokesperson Dr. Lars Klareskog of Karolinska Institutet,

Stockholm. " We may thereby be given some new opportunities to both

predict and understand the onset of RA and to interfere with RA-

inducing events before clinical symptoms are apparent. "

http://www.eurekalert.org/pub_releases/2006-01/jws-tio010306.php