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. 2024 Feb 14;95(3):241-248.
doi: 10.1136/jnnp-2023-332121.

Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort

Stephen A Goutman  1   2 , Jonathan Boss  3 , Dae-Gyu Jang  1   2 , Bhramar Mukherjee  3 , Rudy J Richardson  1   4 , Stuart Batterman  4 , Eva L Feldman  5   2
Affiliations

Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort

Stephen A Goutman et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurogenerative disease caused by combined genetic susceptibilities and environmental exposures. Identifying and validating these exposures are of paramount importance to modify disease risk. We previously reported that persistent organic pollutants (POPs) associate with ALS risk and survival and aimed to replicate these findings in a new cohort.

Method: Participants with and without ALS recruited in Michigan provided plasma samples for POPs analysis by isotope dilution with triple quadrupole mass spectrometry. ORs for risk models and hazard ratios for survival models were calculated for individual POPs. POP mixtures were represented by environmental risk scores (ERS), a summation of total exposures, to evaluate the association with risk (ERSrisk) and survival (ERSsurvival).

Results: Samples from 164 ALS and 105 control participants were analysed. Several individual POPs significantly associated with ALS, including 8 of 22 polychlorinated biphenyls and 7 of 10 organochlorine pesticides (OCPs). ALS risk was most strongly represented by the mixture effects of OCPs alpha-hexachlorocyclohexane, hexachlorobenzene, trans-nonachlor and cis-nonachlor and an interquartile increase in ERSrisk enhanced ALS risk 2.58 times (p<0.001). ALS survival was represented by the combined mixture of all POPs and an interquartile increase in ERSsurvival enhanced ALS mortality rate 1.65 times (p=0.008).

Conclusions: These data continue to support POPs as important factors for ALS risk and progression and replicate findings in a new cohort. The assessments of POPs in non-Michigan ALS cohorts are encouraged to better understand the global effect and the need for targeted disease risk reduction strategies.

Keywords: ALS; epidemiology; neuroepidemiology.

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Conflict of interest statement

Competing interests: SAG: Listed as an inventor on a patent, issue number US10660895, held by University of Michigan titled “Methods for Treating Amyotrophic Lateral Sclerosis” that targets immune pathways for use in ALS therapeutics. Served on a DSMB and provided scientific advisory for a documentary about ALS. JB: Nothing to declare. D-GJ: Nothing to declare. BM: Nothing to declare. RJR: Nothing to declare. SB: Nothing to declare. ELF: Listed as an inventor on a patent, issue number US10660895, held by University of Michigan titled “Methods for Treating Amyotrophic Lateral Sclerosis” that targets immune pathways for use in ALS therapeutics.

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