Human leukocyte antigen-DR15, low infant sibling exposure and multiple sclerosis: Gene-environment interaction

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The cause of multiple sclerosis (MS) is not yet conclusively known but both genes and the environment are important. A region on chromosome 6, the HLA class II, exerts the single strongest genetic effect but the involvement of the environment is also inescapable and is no better illustrated than by the geographical distribution of the disease. The identity of the environmental factors involved in MS is not known unequivocally but there are a few leading candidates, namely, Epstein-Barr virus, vitamin D and smoking. It has been suggested that low sibling infant exposure (classed as having no older siblings and any younger siblings having an age difference of at least 5 years) increases MS risk (Ponsonby et al, JAMA, 2005). Genetic and environmental factors are not independent. In an intriguing study, van der Mei and colleagues observed that HLA-DRB1*15 (a form of the gene involved in MS on chromosome 6) interacted with low sibling infant exposure to increase MS risk. This result could thus be of importance in disease aetiology but requires replication. Other groups have been unable to support an effect of low infant sibling exposure on the risk of MS (Sadovnick et al, Lancet Neurol, 2005; Bager et al, Am J Epidemiol, 2006) so the gene-environment interaction uncovered by van der Mei and others may be specific to Australia; this will require confirmation.

Dr Sreeram Ramagopalan

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