UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
Genetic Epidemiology and Genomics Laboratory, Divisions of Epidemiology and Biostatistics, School of Public Health, University of California Berkeley, Berkeley, California, USA.
J Neurol Neurosurg Psychiatry. 2023 Jul;94(7):518-525. doi: 10.1136/jnnp-2022-330713. Epub 2023 Feb 1.
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 and the absence of and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including (rs2069852), (rs2187163) and (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 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.
The presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.
我们之前曾报告过家庭化学暴露与儿童发病多发性硬化症风险增加之间存在关联。
使用病例对照儿童多发性硬化症研究，估计了家庭化学暴露与儿童发病多发性硬化症风险的基因-环境相互作用。感兴趣的遗传危险因素包括两个主要的 HLA 多发性硬化症危险因素， 和 的存在和缺失，以及常见家庭有毒化学物质代谢途径中的多发性硬化症风险变异，包括 （rs2069852）、 （rs2187163）和 （rs7665090）。
490 例儿童发病多发性硬化症病例和 716 例对照纳入分析。暴露于防蜱虫或蚊虫的驱虫剂（比值比 1.47，95%置信区间 1.06 至 2.04，p=0.019）、除草产品（比值比 2.15，95%置信区间 1.51 至 3.07，p<0.001）和植物/树木病虫害防治产品（比值比 3.25，95%置信区间 1.92 至 5.49，p<0.001）与儿童发病多发性硬化症的发病几率增加相关。暴露于除草产品与 SNP GG 之间存在显著的相加交互作用（归因比例（AP）0.48，95%置信区间 0.10 至 0.87），暴露于植物/病虫害防治产品与 缺失之间存在显著的相加交互作用（AP 0.56；95%置信区间 0.03 至 1.08）。暴露于除草产品与 SNP GG 基因型之间存在乘法交互作用（比值比 2.30，95%置信区间 1.00 至 5.30），但与其他暴露和风险变异无交互作用。未发现与 和 SNP GG 基因型存在交互作用。
家庭毒素的基因-环境相互作用的存在支持它们在儿童发病多发性硬化症中的可能因果作用。
