A new large population-based study from Karolinska Institutet has examined the gene-environment interaction between smoking and SE alleles in rheumatoid arthritis (RA). The study, which is published in the journal Arthritis & Rheumatism, shows that all SE alleles strongly interact with smoking in conferring an increased risk of so called ACPA-positive RA.
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) has been found for the HLA-DRB1 gene, and this site seems to play a central role in susceptibility to the disease, particular in Caucasian populations. 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 RA and are seen only in ACPA-positive patients.
The recently published 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 risk factors and smoking is evident," says Postgraduate Emeli Lundström, who led the study.
Lundström E, Källberg H, Alfredsson L, Klareskog L, Padyukov L.Gene-environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: All alleles are important
Arthritis & Rheumatism, 2009 May 28;60(6):1597-1603