Litvan Irene, Proudfoot James A, Martin Eden R, Standaert David, Riley David, Hall Deborah, Marras Connie, Bayram Ece, Dubinsky Richard M, Bordelon Yvette, Reich Stephen, Shprecher David, Kluger Benzi, Cunningham Christopher, Schellenberg Gerard D, Jankovic Joseph
Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, La Jolla, CA, United States.
Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA, United States.
Front Neurol. 2021 Apr 9;12:664796. doi: 10.3389/fneur.2021.664796. eCollection 2021.
Several genetic and environmental factors have been reported in progressive supranuclear palsy (PSP), although none were identified as a definitive cause. We aimed to explore potential gene-environment interactions in PSP. Two hundred and ninety two PSP cases and 292 controls matched for age, sex, and race from the ENGENE-PSP were analyzed to determine the association between PSP and minor alleles of 5 single nucleotide polymorphisms (SNPs) in 4 genes (MAPT, MOBP, EIF2AK3, and STX6), which were previously associated with PSP risk. Interactions between these SNPs and environmental factors, including previously reported occupational and agricultural risk factors for PSP, were assessed for PSP odds and age of symptom onset. Minor alleles of MAPTrs242557 and EIF2AK3rs7571971 were individually associated with increased odds; MAPTrs8070723 minor alleles were associated with lower PSP odds. There were several gene-environment interactions for PSP odds and age of symptom onset, however, they did not remain significant after FDR-correction. Larger scale studies are required to determine potential interactions.
尽管尚未确定明确病因，但已有报道指出多种遗传和环境因素与进行性核上性麻痹（PSP）有关。我们旨在探索PSP中潜在的基因-环境相互作用。对来自ENGENE-PSP研究的292例PSP病例和292例年龄、性别和种族相匹配的对照进行分析，以确定PSP与4个基因（MAPT、MOBP、EIF2AK3和STX6）中5个单核苷酸多态性（SNP）的次要等位基因之间的关联，这些基因先前与PSP风险相关。评估这些SNP与环境因素之间的相互作用，包括先前报道的PSP职业和农业风险因素，以确定PSP比值比和症状出现年龄。MAPTrs242557和EIF2AK3rs7571971的次要等位基因分别与比值比增加相关；MAPTrs8070723次要等位基因与较低的PSP比值比相关。在PSP比值比和症状出现年龄方面存在多种基因-环境相互作用，然而，在进行FDR校正后，它们不再具有显著性。需要更大规模的研究来确定潜在的相互作用。
