Gene-environment interactions increase the risk of paediatric-onset multiple sclerosis associated with household chemical exposures.

Abstract

We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis. Using a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of <i>DRB1*15</i> and the absence of <i>A*02,</i> and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including <i>IL-6</i> (rs2069852), <i>BCL-2</i> (rs2187163) and <i>NFKB1</i> (rs7665090). 490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p<0.001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p<0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and <i>NFKB1</i> SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of <i>HLA-A*02</i> (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and <i>NFKB1</i> SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with <i>IL-6</i> and <i>BCL-2</i> SNP GG genotypes. The presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.