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



The risk for development of multiple sclerosis has been associated with human leukocyte antigen-DRB1*1501-DQB1*0602 (HLA-DR15) genotype, low infant sibling exposure, and high Epstein–Barr nuclear antigen IgG levels. In a population-based case–control study (Tasmania, Australia), we found that the combined effect of HLA-DR15 positivity and low infant sibling exposure on multiple sclerosis (odds ratio, 7.88; 95% confidence interval, 3.43–18.11) was 3.9-fold greater than expected (test for interaction, p = 0.019) This interaction was observed irrespective of Epstein–Barr nuclear antigen IgG levels. This suggests that immune mechanisms involving HLA class II molecules are susceptible to modulation in early life. Ann Neurol 2009;66:261–265 ANN NEUROL 2010;67:259–263