■肌萎缩侧索硬化症(ALS)的发病机制涉及遗传和环境因素。这项研究调查了血浆和尿液中金属测量值之间的关联,ALS风险和生存,和曝光源。
■来自密歇根州的有和没有ALS的参与者提供了血浆和尿液样品,用于通过电感耦合等离子体质谱法进行金属测量。使用风险和生存模型计算每种金属的赔率和风险比。创建环境风险评分(ERS)以评估暴露混合物与ALS风险与生存和暴露源之间的关联。ALS(ALS-PGS)和金属(金属-PGS)多基因风险评分是从独立的全基因组关联研究和相关文献选择的SNP构建的。
■分析了来自454名ALS和294名对照参与者的血浆和尿液样本。单个金属的水平升高,包括铜,硒,还有锌,与ALS风险和生存率显著相关。代表与ALS风险密切相关的金属混合物的ERS(血浆,OR=2.95,CI=2.38-3.62,p<0.001;尿液,OR=3.10,CI=2.43-3.97,p<0.001)和较差的ALS生存率(血浆,HR=1.42,CI=1.24-1.63,p<0.001;尿液,HR=1.52,CI=1.31-1.76,p<0.001)。ALS-PGS或金属-PGS的添加并没有改变具有ALS风险和存活的金属的重要性。与升高的ERS相关的具有高金属暴露潜力的职业。此外,与测量的血浆和尿液金属相关的职业性和非职业性金属暴露。
■血浆和尿液中的金属与ALS风险增加和生存率降低有关,独立于遗传风险,并与职业性和非职业性金属暴露相关。这些数据强调了金属暴露在ALS风险和进展中的重要性。
UNASSIGNED: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival, and exposure sources.
UNASSIGNED: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. Odds and hazard ratios for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected SNPs.
UNASSIGNED: Plasma and urine samples from 454 ALS and 294 control participants were analyzed. Elevated levels of individual metals, including copper, selenium, and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62, p<0.001; urine, OR=3.10, CI=2.43-3.97, p<0.001) and poorer ALS survival (plasma, HR=1.42, CI=1.24-1.63, p<0.001; urine, HR=1.52, CI=1.31-1.76, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures associated with measured plasma and urine metals.
UNASSIGNED: Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.