Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders
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
Parkinsonism & related disorders
Digital Object Identifier (DOI)
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.