Journal Article

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

Waldman, Amy T, Aaen, Gregory, Mesaros, Clementina, Ziaei, Amin, Rensel, Mary, Mar, Soe, Simpson-Yap, Steve, Krupp, Lauren, Barcellos, Lisa F, Weinstock-Guttman, Bianca, Graves, Jennifer S, Hart, Janace, Waltz, Michael, Tillema, Jan-Mendelt, Nasr, Zahra, Casper, T Charles, Rose, John, Schreiner, Teri, Chitnis, Tanuja, Lotze, Tim, Benson, Leslie, Greenberg, Benjamin, Adams, Cameron, Waubant, Emmanuelle, Schoeps, Vinicius Andreoli, Virupakshaiah, Akash, Rodriguez, Moses

2023

Overview

BackgroundWe previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis.MethodsUsing 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 DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090).Results490 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 NFKB1 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 HLA-A*02 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 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 IL-6 and BCL-2 SNP GG genotypes.ConclusionsThe presence of gene–environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD
• Subject: Age / Alzheimer's disease / Case-Control Studies / Chemicals / Child / Disease control / Education / Ethnicity / Gene expression / Gene-Environment Interaction / Genes / Genetic Predisposition to Disease - genetics / genetics / Genotype / Genotype & phenotype / Health risk assessment / HLA Antigens / HLA-DRB1 Chains - genetics / Households / Humans / Interleukin-6 / Multiple sclerosis / Multiple Sclerosis - chemically induced / Multiple Sclerosis - epidemiology / Multiple Sclerosis - genetics / paediatric neurology / Pediatrics / Proto-Oncogene Proteins c-bcl-2 - genetics / Regression analysis / Risk Factors / Trees / Weeds