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

BACKGROUND

We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.

METHODS

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 and the absence of and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including (rs2069852), (rs2187163) and (rs7665090).

RESULTS

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 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 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and 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 and SNP GG genotypes.

CONCLUSIONS

The presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.