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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.
- ALS
- epidemiology
- neuroepidemiology
Data availability statement
Data are available upon reasonable request. Sharing of non-identifiable data will be considered at the reasonable request of a qualified investigator. Request should be made to the corresponding author and requires the submission of a proposal to be approved by a study committee and an institutionally signed data sharing agreement.
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Data availability statement
Data are available upon reasonable request. Sharing of non-identifiable data will be considered at the reasonable request of a qualified investigator. Request should be made to the corresponding author and requires the submission of a proposal to be approved by a study committee and an institutionally signed data sharing agreement.
Footnotes
Contributors SAG and JB directly accessed and verified the underlying clinical data reported in the manuscript. SAB and JB directly accessed and verified the underlying persistent organic pollutant data reported in the manuscript. All authors had full access to all the data in the study and accept responsibility to submit for publication. SAG: Conceptualisation, funding acquisition, investigation, writing—original draft. JB: Formal analysis, writing—review and editing. D-GJ: Formal analysis, writing—review and editing. BM: Formal analysis, writing—review and editing. RJR: Literature search, writing—review and editing. SB: Conceptualisation, funding acquisition, investigation, writing—review and editing. ELF: Conceptualisation, funding acquisition, investigation, resources, supervision, writing—review and editing, guarantor.
Funding National ALS Registry/CDC/ATSDR (1R01TS000289); National ALS Registry/CDC/ATSDR CDCP-DHHS-US (CDC/ATSDR 200-2013-56856); NIEHS K23ES027221; NIEHS R01ES030049; NINDS (R01NS127188), NeuroNetwork for Emerging Therapies, the NeuroNetwork Therapeutic Discovery Fund, the Peter R. Clark Fund for ALS Research, the Sinai Medical Staff Foundation, Scott L. Pranger, University of Michigan; National Center for Advancing Translational Sciences at the National Institutes of Health (UL1TR002240).
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.
Provenance and peer review Not commissioned; externally peer reviewed.
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