Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders

Authors

Susan Searles Nielsen, University of Washington, Department of Neurology, Seattle, WA, USA; University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA, USA. Electronic address: ssn@uw.edu.
Harvey Checkoway, University of California San Diego, Department of Family and Preventive Medicine, La Jolla, CA, USA.
Susan R. Criswell, Washington University, Department of Neurology, St. Louis, MO, USA.
Federico M. Farin, University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA, USA.
Patricia L. Stapleton, University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA, USA.
Lianne Sheppard, University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, WA, USA; University of Washington, Department of Biostatistics, Seattle, WA, USA.
Brad A. Racette, Washington University, Department of Neurology, St. Louis, MO, USA; University of the Witwatersrand, School of Public Health, Parktown, South Africa.

Document Type

Article

Abstract

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.

Medical Subject Headings

Adult; Aged; DNA Methylation; Humans; Male; Manganese (adverse effects); Middle Aged; Nitric Oxide Synthase Type II (metabolism); Occupational Diseases (chemically induced); Occupational Exposure (adverse effects); Parkinson Disease, Secondary (chemically induced); Welding

Publication Date

4-1-2015

Publication Title

Parkinsonism & related disorders

E-ISSN

1873-5126

Volume

21

Issue

4

First Page

355

Last Page

60

PubMed ID

25634431

Digital Object Identifier (DOI)

10.1016/j.parkreldis.2015.01.007

Recommended Citation

Searles Nielsen, Susan; Checkoway, Harvey; Criswell, Susan R.; Farin, Federico M.; Stapleton, Patricia L.; Sheppard, Lianne; and Racette, Brad A., "Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders" (2015). Neurology. 1139.
https://scholar.barrowneuro.org/neurology/1139