Kaliforniya Merkez Vadisi'nde Parkinson hastalığı olan ve olmayan tarımsal bakır pestisit maruziyeti ve DNA metilasyonu.

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BackgroundCopper-induced oxidative damage and mitochondrial dysfunction may exacerbate Parkinson's disease (PD) pathology. DNA methylation (DNAm) can serve as a biological mediator of environmental exposures.ObjectiveTo investigate the impact of chronic, long-term copper exposure on genome-wide DNA methylation patterns in the blood of PD cases and community controls.MethodsWe analyzed 806 blood samples (569 PD cases and 237 controls) from a population-based case-control study. Epigenome-wide association analysis (EWAS) was conducted to identify differentially methylated probes (DMPs) and regions (DMRs), adjusting for age, sex, European ancestry, smoking status, study wave, cell composition, and organophosphates (OP) exposure. In addition, overrepresentation analyses were conducted to identify enriched pathways and biological functions.ResultsWe identified 140 CpG sites and 40 genomic regions that were associated with copper pesticide exposure, including cg17591573 (r = -0.16, p = 8.84E-09) in the COL11A2 gene, cg11538176 in UBE3C (r = -0.18, p = 9.26E-09), cg11208322 in MAGI2 (r = -0.15, p = 1.00E-08) and a region located on chromosome 1 (bp start site 205818668; ends 205819609). DMP and DMR gene set enrichment analyses identified as the most enriched pathways Fc gamma R-mediated phagocytosis (p = 6.03E-05, FDR = 2.17E-02) and homophilic cell adhesion via plasma membrane adhesion molecules (p = 2.27E-07, FDR = 5.08E-03).ConclusionWe found evidence that long-term ambient exposure to copper pesticides resulted in differential DNA methylation in blood of PD patients and elderly controls. Chronic copper pesticide exposure may affect multiple pathways, specifically phagocytosis pathway, EGF receptor signaling pathway, and homophilic cell adhesion mechanisms that are relevant to neuroinflammation and neurodegeneration in PD.

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