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Smoking and genetics play role in rheumatoid arthritis

October 22, 2015

"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," 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.

interscience.wiley/