Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study.

IF 8.7 1区医学 Q1 CLINICAL NEUROLOGY Journal of Neurology, Neurosurgery, and Psychiatry Pub Date : 2024-08-06 DOI:10.1136/jnnp-2024-333978

Dae-Gyu Jang, John F Dou, Emily J Koubek, Samuel Teener, Lili Zhou, Kelly M Bakulski, Bhramar Mukherjee, Stuart A Batterman, Eva L Feldman, Stephen A Goutman

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Abstract

Background: 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.

Methods: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs 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 single-nucleotide polymorphisms.

Results: Plasma and urine samples from 454 ALS and 294 control participants were analysed. 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=1.37, CI=1.20-1.58, p<0.001; urine, HR=1.44, CI=1.23-1.67, 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 were associated with measured plasma and urine metals.

Conclusion: 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.

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与遗传风险无关的多种金属暴露与肌萎缩性脊髓侧索硬化症的高风险和死亡率相关，并与自我报告的暴露相关：一项病例对照研究。

背景：肌萎缩性脊髓侧索硬化症（ALS）的发病机制涉及遗传和环境因素。本研究调查了血浆和尿液中的金属含量、ALS 风险和存活率以及暴露源之间的关联：方法：密歇根州的 ALS 患者和非 ALS 患者提供血浆和尿液样本，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了每种金属的ORs和HRs。创建了环境风险评分 (ERS)，以评估暴露混合物与 ALS 风险、存活率和暴露源之间的关联。ALS（ALS-PGS）和金属（metal-PGS）多基因风险评分是根据一项独立的全基因组关联研究和相关文献选择的单核苷酸多态性构建的：对 454 名 ALS 患者和 294 名对照组患者的血浆和尿液样本进行了分析。包括铜、硒和锌在内的单个金属水平升高与 ALS 风险和存活率有显著相关性。代表金属混合物的 ERS 与 ALS 风险密切相关（血浆，OR=2.95，CI=2.38-3.62，p）：血浆和尿液中的金属与 ALS 风险增加和存活率降低有关，与遗传风险无关，并与职业和非职业金属暴露相关。这些数据强调了金属暴露在 ALS 风险和进展中的重要性。

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来源期刊

Journal of Neurology, Neurosurgery, and Psychiatry 医学-精神病学

CiteScore

15.70

自引率

1.80%

发文量

888

审稿时长

6 months

期刊介绍： The Journal of Neurology, Neurosurgery & Psychiatry (JNNP) aspires to publish groundbreaking and cutting-edge research worldwide. Covering the entire spectrum of neurological sciences, the journal focuses on common disorders like stroke, multiple sclerosis, Parkinson’s disease, epilepsy, peripheral neuropathy, subarachnoid haemorrhage, and neuropsychiatry, while also addressing complex challenges such as ALS. With early online publication, regular podcasts, and an extensive archive collection boasting the longest half-life in clinical neuroscience journals, JNNP aims to be a trailblazer in the field.