PMID- 37758454
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240502
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Print)
IS  - 0022-3050 (Linking)
VI  - 95
IP  - 3
DP  - 2024 Feb 14
TI  - Environmental risk scores of persistent organic pollutants associate with higher 
      ALS risk and shorter survival in a new Michigan case/control cohort.
PG  - 241-248
LID - 10.1136/jnnp-2023-332121 [doi]
AB  - 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 (ERS(risk)) and survival 
      (ERS(survival)). 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 ERS(risk) 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 ERS(survival) 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.
CI  - (c) Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Goutman, Stephen A
AU  - Goutman SA
AUID- ORCID: 0000-0001-8780-6637
AD  - Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
AD  - NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, Michigan, 
      USA.
FAU - Boss, Jonathan
AU  - Boss J
AD  - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
FAU - Jang, Dae-Gyu
AU  - Jang DG
AUID- ORCID: 0009-0009-7966-1322
AD  - Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
AD  - NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, Michigan, 
      USA.
FAU - Mukherjee, Bhramar
AU  - Mukherjee B
AD  - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
FAU - Richardson, Rudy J
AU  - Richardson RJ
AUID- ORCID: 0000-0002-2028-5723
AD  - Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
AD  - Department of Environmental Health Sciences, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Batterman, Stuart
AU  - Batterman S
AUID- ORCID: 0000-0001-9894-5325
AD  - Department of Environmental Health Sciences, University of Michigan, Ann Arbor, 
      Michigan, USA.
FAU - Feldman, Eva L
AU  - Feldman EL
AUID- ORCID: 0000-0002-9162-2694
AD  - Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA 
      efeldman@umich.edu.
AD  - NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, Michigan, 
      USA.
LA  - eng
GR  - R01 TS000289/TS/ATSDR CDC HHS/United States
GR  - R01TS000289/ACL/ACL HHS/United States
GR  - K23 ES027221/ES/NIEHS NIH HHS/United States
GR  - R01 ES030049/ES/NIEHS NIH HHS/United States
GR  - UL1 TR002240/TR/NCATS NIH HHS/United States
GR  - R01 NS127188/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20240214
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 3734-49-4 (nonachlor)
RN  - 0 (Persistent Organic Pollutants)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - Amyotrophic lateral sclerosis 1
SB  - IM
MH  - Humans
MH  - Persistent Organic Pollutants
MH  - Michigan/epidemiology
MH  - *Amyotrophic Lateral Sclerosis
MH  - *Environmental Pollutants/adverse effects
MH  - Risk Factors
MH  - *Hydrocarbons, Chlorinated
PMC - PMC11060633
MID - NIHMS1985903
OTO - NOTNLM
OT  - ALS
OT  - epidemiology
OT  - neuroepidemiology
COIS- 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.
EDAT- 2023/09/28 00:42
MHDA- 2024/02/16 06:43
PMCR- 2025/02/14
CRDT- 2023/09/27 21:03
PHST- 2023/06/30 00:00 [received]
PHST- 2023/09/05 00:00 [accepted]
PHST- 2025/02/14 00:00 [pmc-release]
PHST- 2024/02/16 06:43 [medline]
PHST- 2023/09/28 00:42 [pubmed]
PHST- 2023/09/27 21:03 [entrez]
AID - jnnp-2023-332121 [pii]
AID - 10.1136/jnnp-2023-332121 [doi]
PST - epublish
SO  - J Neurol Neurosurg Psychiatry. 2024 Feb 14;95(3):241-248. doi: 
      10.1136/jnnp-2023-332121.