Hedström et al. Brain. 2011 Mar;134(Pt 3):653-64. Epub 2011 Feb 8.
As you know from previous postings both genetic and environmental factors are associated with MS. Gene-environment interactions may exert stronger effects.
In this study, the investigators studied potential interactions between genetic risk factors and smoking in relation to risk of developing MS. Results: a significant interaction between two genetic risk factors was found; smokers who had inherited a particular human leukocyte antigen DRB1*15 were less likely to inherit another leukocyte antigen A*02; the interaction between these two genetic factors was absent among non-smokers. Importantly, compared with non-smokers with neither of the genetic risk factors, smokers with both genetic risk factor were 13.5x more likely to get MS. For smokers without the genetic risk there chances were only 1.4x. For non-smokers with both genetic risk factors there risk was 4.9x greater than the background risk. Conclusion: The risk of developing MS associated with specific human leukocyte antigens is strongly influenced by smoking status.
"How these interactions lead to an increased risk of MS is unknown. Clearly we need to explain this if we want to understand the cause of MS."