Grantee Research Project Results
Air pollution and homocysteine: more evidence that oxidative stress-related genes modify effects of particulate air pollution.
Citation:
Ren C, Park SK, Vokonas PS, Sparrow D, Wilker E, Baccarelli A, Suh HH, Tucker KL, Wright RO, Schwartz J. Air pollution and homocysteine: more evidence that oxidative stress-related genes modify effects of particulate air pollution. Epidemiology 2010;21(2):198-206.
Abstract:
BACKGROUND: Ambient particles are associated with cardiovascular events and recently with total plasma homocysteine. High total plasma homocysteine is a risk for human health. However, the biologic mechanisms are not fully understood. One of the putative pathways is through oxidative stress. We aimed to examine whether associations of PM2.5 and black carbon with homocysteine were modified by genotypes including HFE H63D, C282Y, CAT (rs480575, rs1001179, rs2284367, and rs2300181), NQO1 (rs1800566), GSTP1 I105V, GSTM1, GSTT1 (deletion vs. nondeletion), and HMOX-1 (any short vs. both long). We attempted to replicate identified genes in an analysis of heart rate variability and in other outcomes reported in the literature. METHODS: Study subjects were 1000 white non-Hispanic men in the Boston area, participating in a cohort study of aging. PM2.5 , black carbon, total plasma homocysteine, and other covariates were measured at several points in time between 1995 and 2006. We fit mixed models to examine effect modification of genes on associations of pollution with total plasma homocysteine. RESULTS: Interquartile range increases in PM2.5 and black carbon (7-day moving averages) were associated with 1.5% (95% confidence interval = 0.2% to 2.8%) and 2.2% (0.6% to 3.9%) increases in total plasma homocysteine, respectively. GSTT1 and HFE C282Y modified effects of black carbon on total plasma homocysteine, and HFE C282Y and CAT (rs2300181) modified effects of PM2.5 on homocysteine. Several genotypes marginally modified effects of PM2.5 and black carbon on various endpoints. All genes with significant interactions with particulate air pollution had modest main effects on total plasma homocysteine. CONCLUSIONS: Effects of PM2.5 and black carbon on various endpoints appeared to be mediated by genes related to oxidative stress pathways.The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.