Genes and smoking play role in rheumatoid arthritis

Jun 01, 2009

Recent genetic studies have revealed several new sites of genes that are risk factors for developing rheumatoid arthritis (RA). The strongest association with anti-citrullinated protein antibody (ACPA)-positive RA (ACPAs are autoantibodies detected in RA that are used as a major diagnostic tool) has been found for the HLA-DRB1 gene, and this site seems to play a central role in susceptibility to the disease in Caucasian populations. Previous studies have shown a high increase in the risk of ACPA-positive RA associated with smoking in those who have certain variations of the HLA-DRB1 gene. There are several types of such alleles related to a particular amino acid sequence known as shared epitope (SE). ACPAs occur in about 60 percent of RA patients and are closely linked to the presence of SE alleles. In fact, SE alleles are the strongest genetic risk factor for ACPA-positive RA.

Of several environmental factors that predispose people toward developing RA, smoking has been found to be the main risk factor and a strong gene-environment interaction between smoking and SE alleles for ACPA-positive patients has been shown in previous studies in Europe. Results in North America have not been as conclusive, however. A new large population-based study examined the gene-environment interaction between smoking and SE alleles in RA and found that all SE alleles strongly interact with smoking in conferring an increased risk of ACPA-positive RA. The study was published in the June issue of Arthritis & Rheumatism .

Led by Emeli Lundström of Karolinska Institutet in Stockholm, the study consisted of genetic analysis of 1,319 RA cases and 943 controls in Sweden and included Caucasian smokers and non-smokers. Researchers set out to determine whether all HLA-DRB1 SE alleles demonstrated a similar gene-environment interaction or if the interaction was restricted to a particular DRB1 SE group. A total of 972 cases and 488 controls were SE positive.

"Our data illustrate that regardless of the fine specificity of the SE alleles of DRB1, the interaction between these genetic and smoking is evident," the authors state.

Although the molecular mechanisms underlying the risk and interaction of smoking and SE alleles are incompletely understood, there are several possible explanations. One is that long-term exposure to cigarette smoke may accelerate the modification of arginine into citrulline in autoantigens present in the lungs, enhancing an immune response in individuals carrying the SE alleles. Another possibility is that substances present in smoke may trigger the innate immune system to contribute to the development of arthritis. It may also be that an as yet undetermined genetic factor (factors) plays a role or that there is a genetic interaction between the HLA-DRB1 gene and the gene involved in the behavior that includes smoking.

The authors conclude that while SE alleles do not seem to confer an increased risk of ACPA-negative RA either on their own or in combination with smoking, all SE DRB1 alleles strongly interact with smoking in the development of ACPA-positive RA.

More information: "Gene-Environment Interaction Between the DRB1 Shared Epitope and Regarding the Risk of Anti-Citrullinated Antibody-Positive ," Emeli Lundström, Henrik Källberg, Lars Alfredsson, Lars Klareskog, Leonid Padyukov, Arthritis & Rheumatism, June 2009. http://www3.interscience.wiley.com/journal/76509746/home

Source: Wiley (news : web)

Explore further: Recorded Ebola deaths top 7,000

add to favorites email to friend print save as pdf

Related Stories

The HLA-DRB1 gene and premature death in rheumatoid arthritis

Jan 31, 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 ...

Recommended for you

Recorded Ebola deaths top 7,000

5 hours ago

The worst Ebola outbreak on record has now killed more than 7,000 people, with many of the latest deaths reported in Sierra Leone, the World Health Organization said as United Nations Secretary-General Ban ...

Liberia holds Senate vote amid Ebola fears (Update)

9 hours ago

Health workers manned polling stations across Liberia on Saturday as voters cast their ballots in a twice-delayed Senate election that has been criticized for its potential to spread the deadly Ebola disease.

Evidence-based recs issued for systemic care in psoriasis

Dec 19, 2014

(HealthDay)—For appropriately selected patients with psoriasis, combining biologics with other systemic treatments, including phototherapy, oral medications, or other biologic, may result in greater efficacy ...

Bacteria in caramel apples kills at least four in US

Dec 19, 2014

A listeria outbreak believed to originate from commercially packaged caramel apples has killed at least four people in the United States and sickened 28 people since November, officials said Friday.

Steroid-based treatment may answer needs of pediatric EoE patients

Dec 19, 2014

A new formulation of oral budesonide suspension, a steroid-based treatment, is safe and effective in treating pediatric patients with eosinophilic esophagitis (EoE), according to a new study in Clinical Gastroenterology and Hepatology, the official clinical practice journal ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.