system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Air Pollutants, Blood Coagulation, Blood Coagulation Disorders, Confidence Intervals, DNA Methylation, Endothelin-1, Gene Expression Regulation, Humans, Industry, Inflammation, Inhalation Exposure, Leukocytes, Male, Middle Aged, Nitric Oxide Synthase Type III, Occupational Diseases, Occupational Exposure, Particulate Matter, Thrombosis, Zinc.
user
Does blood hypomethylation of inflammatory genes mediate the effects of metal-rich airborne pollutants on blood coagulation? Context: Recent investigations have associated airborne particulate matter (PM) with increased coagulation and thrombosis, but underlying biological mechanisms are still incompletely characterised. DNA methylation is an environmentally sensitive mechanism of gene regulation that could potentially contribute to PM-induced hypercoagulability. We aimed to test whether altered methylation mediates environmental effects on coagulation. We investigated 63 steel workers exposed to a wide range of PM levels, as a work-related condition with well-characterised prothrombotic exposure. We measured personal PM10 (PM≤10 µm in aerodynamic diameter), PM1 (≤1 µm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitric-oxide-synthase-3) and EDN1 (endothelin-1) through bisulfite-pyrosequencing and we measured ETP as a global coagulation-activation test after standardised triggers. ETP increased in association with PM10 (β=20.0, 95% CI 3.0 to 37.0), PM1 (β=80.8 95% CI 14.9 to 146.7) and zinc (β=51.3, 95% CI 0.01 to 111.1) exposures. NOS3 methylation was negatively associated with PM10 (β=-0.2, 95% CI -0.4 to -0.03), PM1 (β=-0.8, 95% CI -1.4 to -0.1), zinc (β=-0.9, 95% CI -1.4 to -0.3) and iron (β=-0.7, 95% CI -1.4 to -0.01) exposures. Zinc exposure was negatively associated with EDN1 (β=-0.3, 95% CI -0.8 to -0.1) methylation. Lower NOS3 (β=-42.3; p<0.001) and EDN1 (β=-14.5; p=0.05) were associated with higher ETP. Statistical mediation analysis formally confirmed NOS3 and EDN1 hypomethylation as intermediate mechanisms for PM-related coagulation effects.
assistant
Our study showed for the first time, that gene hypomethylation contributes to environmentally induced hypercoagulability. Final Decision: yes