Inducible Nitric Oxide Synthase Gene Methylation and Parkinsonism in Manganese-Exposed Welders

Details

• Personal Author:
  Checkoway, Harvey ; Criswell SR ; Farin FM ; Racette BA ; Seales Nielsen S ; Sheppard L ; Stapleton PL
• Description:
  Introduction: Neurologist-assessed parkinsonism signs are prevalent among workers exposed to manganese (Mn)-containing welding fume. Neuroinflammation may possibly play a role. Inducible nitric oxide synthase, coded by NOS2, is involved in inflammation, and particulate exposure increases the gene's expression through methylation of CpG sites in the 5' region. Methods: We assessed DNA methylation at three CpG sites in the NOS2 exon 1 from blood from 201 welders. All were non-Hispanic Caucasian men 25-65 years old who were examined by a neurologist specializing in movement disorders. We categorized the workers according to their Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3) scores as parkinsonism cases (UPDRS3 = 15; n = 49), controls (UPDRS3 < 6; n = 103), or intermediate (UPDRS3 = 6 to < 15; n = 49). Results: While accounting for age, examiner and experimental plate, parkinsonism cases had lower mean NOS2 methylation than controls (p-value for trend = 0.04), specifically at CpG site 8329 located in an exonic splicing enhancer of NOS2 (p-value for trend = 0.07). These associations were not observed for the intermediate UPDRS3 group (both p-value for trend = 0.59). Conclusions: Inflammation mediated by inducible nitric oxide synthase may possibly contribute to the association between welding fume and parkinsonism, but requires verification in a longitudinal study. [Description provided by NIOSH]
• Subjects:
  Manganese Occupational Exposure Occupational Health Safety Welding
• Keywords:
  Author Keywords: DNA Methylation Biological Effects Central Nervous System Nitric Oxide Synthase Type II Occupational Exposure Parkinsonian Disorders Parkinsonism Welders Welding Fumes
• ISSN:
  1353-8020
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Missouri ; OSHA Region 10 ; OSHA Region 7 ; OSHA Region 9 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  355-360
• Volume:
  21
• Issue:
  4
• NIOSHTIC Number:
  nn:20054805
• Citation:
  Parkinsonism Relat Disord 2015 Apr; 21(4):355-360
• Contact Point Address:
  Susan Searles Nielsen, University of Washington, Department of Neurology, Box 359775, Seattle, WA, 98195-9775, USA
• Email:
  ssn@uw.edu
• CAS Registry Number:
  Manganese (CAS RN 7439-96-5) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2015
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Parkinsonism & Related Disorders
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:45dd7d9190abe47a6747f39d2a8d9e73b8e31a415023f3da81b8d24aa8c224ed6f2246536994a3f8bb1c3e1871ba29dfb8921c23153aabbcebd50248b24e5dde
• Download URL:
  https://stacks.cdc.gov/view/cdc/217235/cdc_217235_DS1.pdf
• File Type:
  [PDF - 118.71 KB ]