Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Eur J Neurol. 2022 Oct;29(10):2956-2966. doi: 10.1111/ene.15475. Epub 2022 Jul 5.
Multiple system atrophy (MSA) has no definitive genetic or environmental (G-E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G-E factors associated with MSA and its subtypes, MSA-P and MSA-C.
A consecutive case-control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model.
A total of 207 MSA patients and 136 healthy controls were enrolled. In addition to SNP COQ2_rs148156462 (TT), MSA risk was correlated with G-E interactions, including COQ2_rs148156462 (Tc) × pesticide nonexposure, COQ2_rs148156462 (TT) × current smokers, SNCA_rs11931074 (tt) × alcohol nonusers, and SNCA_rs11931074 (GG) × well water nondrinkers (all p < 0.01), with an area under the receiver operating characteristic curve (AUC) of 0.804 (95% confidence interval [CI] = 0.671-0.847). Modulated risk of MSA-C, with MSA-P as a control, correlated with COQ2_rs148156462 (TT) × alcohol nondrinkers, SNCA_rs11931074 (GG) × well water ever drinkers, SNCA_rs11931074 (Gt) × well water never drinkers, and SNCA_rs3857059 (gg) × pesticide nonexposure (all p < 0.05), with an AUC of 0.749 (95% CI = 0.683-0.815).
Certain COQ2 and SNCA SNPs interact with common environmental factors to modulate MSA etiology and subtype disposition. The mechanisms underlying the observed correlation between G-E interactions and MSA etiopathogenesis warrant further investigation.
多系统萎缩（MSA）没有明确的遗传或环境（G-E）危险因素，这些因素的综合影响对 MSA 病因仍不清楚。本研究旨在探讨与 MSA 及其亚型 MSA-P 和 MSA-C 相关的 G-E 因素的综合效应。
在两家医疗中心进行了一项连续病例对照研究，通过逐步逻辑回归模型分析了五个先前报道的易感单核苷酸多态性（SNP；SNCA_rs3857059、SNCA_rs11931074、COQ2_rs148156462、EDN1_rs16872704、MAPT_rs9303521）的基因型与四个环境因素（吸烟、饮酒、饮用井水、农药暴露）的分级暴露（从不、曾经、当前）之间的相互作用。
共纳入 207 例 MSA 患者和 136 例健康对照者。除 SNP COQ2_rs148156462（TT）外，MSA 风险与 G-E 相互作用相关，包括 COQ2_rs148156462（Tc）×无农药暴露、COQ2_rs148156462（TT）×当前吸烟者、SNCA_rs11931074（tt）×非饮酒者和 SNCA_rs11931074（GG）×非饮用井水者（均 P＜0.01），受试者工作特征曲线（ROC）下面积（AUC）为 0.804（95%置信区间[CI]：0.671-0.847）。以 MSA-P 为对照，MSA-C 的风险调节与 COQ2_rs148156462（TT）×非饮酒者、SNCA_rs11931074（GG）×曾饮用井水者、SNCA_rs11931074（Gt）×从未饮用井水者和 SNCA_rs3857059（gg）×无农药暴露相关（均 P＜0.05），AUC 为 0.749（95%CI：0.683-0.815）。
某些 COQ2 和 SNCA SNP 与常见环境因素相互作用，调节 MSA 的病因和亚型分布。观察到的 G-E 相互作用与 MSA 发病机制之间的相关性的潜在机制需要进一步研究。
