Highlights
- •We assess methylation of NOS2 in 201 workers exposed to welding fume.
- •Exposure to manganese-containing welding fume is associated with NOS2 methylation.
- •NOS2 methylation is associated with parkinsonism among welders.
- •Inducible nitric oxide synthase may play a role in parkinsonism in welders.
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.
Keywords
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Article info
Publication history
Published online: January 17, 2015
Accepted:
January 11,
2015
Received in revised form:
January 1,
2015
Received:
October 7,
2014
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
