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

• DOI: 10.1136/jnnp-2022-330713
• Publication Date: 2023-02-01T18:26:12Z
• Authors: Zahra Nasr; Vinicius Andreoli...; Amin Ziaei; Akash Virupakshaiah; Cameron Adams; T Charles Casper; Michael Waltz; John Rose; Moses Rodriguez; Jan-Mendelt Tillema; Tanuja Chitnis; Jennifer S Graves; Leslie Benson; Mary Rensel; Lauren Krupp; Amy T Waldman; Bianca Weinstock-...; Tim Lotze; Benjamin Greenberg; Gregory Aaen; Soe Mar; Teri Schreiner; Janace Hart; Steve Simpson-Yap; Clementina Mesaros; Lisa F Barcellos; Emmanuelle Waubant
• Keywords: 0301 basic medicine; Multiple Sclerosis; Genotype; paediatric neurology; 610; multiple sclerosis; Autoimmune Disease; Medical and Health Sciences; 03 medical and health sciences; Clinical Research; Risk Factors; HLA Antigens; Genetics; 2.1 Biological and endogenous factors; Humans; genetics; Genetic Predisposition to Disease; Aetiology; Child; Neurology & Neurosurgery; Interleukin-6; Prevention; Psychology and Cognitive Sciences; Neurosciences; 3. Good health; Brain Disorders; Proto-Oncogene Proteins c-bcl-2; Case-Control Studies; Gene-Environment Interaction; HLA-DRB1 Chains

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