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.
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. ingrid.vandermei@utas.edu.au
Ingrid A F
IA
van der Mei
Arine-Louise
AL
Ponsonby
Bruce V
BV
Taylor
Jim
J
Stankovich
Joanne L
JL
Dickinson
Simon
S
Foote
Andrew
A
Kemp
Terence
T
Dwyer
D000328:Adult; D016022:Case-Control Studies; D004777:Environment; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059810:HLA-DR Serological Subtypes; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000473:pathology / Q000523:psychology; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D035781:Siblings / Q000523:psychology*
D019309:Epstein-Barr Virus Nuclear Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen