Title

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

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

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