Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men

Jaime Madrigano, Andrea Baccarelli, Murray A Mittleman, Robert O Wright, David Sparrow, Pantel S Vokonas, Letizia Tarantini, Joel Schwartz, Jaime Madrigano, Andrea Baccarelli, Murray A Mittleman, Robert O Wright, David Sparrow, Pantel S Vokonas, Letizia Tarantini, Joel Schwartz

Abstract

Background: DNA methylation is a potential pathway linking environmental exposures to disease. Exposure to particulate air pollution has been associated with increased cardiovascular morbidity and mortality, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity.

Objective: We hypothesized that prolonged exposure to particulate pollution would be associated with hypomethylation of repetitive DNA elements and that this association would be modified by genes involved in glutathione metabolism and other host characteristics.

Methods: DNA methylation of the long interspersed nucleotide element-1 (LINE-1) and the short interspersed nucleotide element Alu were measured by quantitative polymerase chain reaction pyrosequencing in 1,406 blood samples from 706 elderly participants in the Normative Aging Study. We estimated changes in repetitive element DNA methylation associated with ambient particles (particulate matter ≤ 2.5 µm in aerodynamic diameter), black carbon (BC), and sulfates (SO₄), with mixed models. We examined multiple exposure windows (1-6 months) before DNA methylation measurement. We investigated whether this association was modified by genotype and phenotype.

Results: An interquartile range (IQR) increase in BC over a 90-day period was associated with a decrease of 0.31% 5-methylcytosine (5mC) (95% confidence interval, 0.12-0.50%) in Alu. An IQR increase in SO₄ over a 90-day period was associated with a decrease of 0.27% 5mC (0.02-0.52%) in LINE-1. The glutathione S-transferase mu-1-null genotype strengthened the association between BC and Alu hypomethylation.

Conclusion: Prolonged exposure to BC and SO₄ particles was associated with hypomethylation of two types of repetitive elements.

Conflict of interest statement

J.S. has served as an expert witness for the U.S. Department of Justice. The authors declare they have no other actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Association between BC and Alu according to time window of exposure and GSTM1 genotype.

References

    1. Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21(2):243–251.
    1. Baccarelli A, Tarantini L, Wright RO, Bollati V, Litonjua AA, Zanobetti A, et al. Repetitive element DNA methylation and circulating endothelial and inflammation markers in the VA Normative Aging Study. Epigenetics. 2010;5(3):222–228. a.
    1. Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, et al. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology. 2010;21(6):819–828. b.
    1. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, et al. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009;179(7):572–578.
    1. Banerjee G, Gupta N, Tiwari J, Raman G. Ultraviolet-induced transformation of keratinocytes: possible involvement of long interspersed element-1 reverse transcriptase. Photodermatol Photoimmunol Photomed. 2005;21(1):32–39.
    1. Bateson TF, Schwartz J. Who is sensitive to the effects of particulate air pollution on mortality? A case-crossover analysis of effect modifiers. Epidemiology. 2004;15(2):143–149.
    1. Belancio VP, Deininger PL, Roy-Engel AM.2009LINE dancing in the human genome: transposable elements and disease. Genome Med 11097doi:[Online 27 October 2009]10.1186/gm97
    1. Belancio VP, Hedges DJ, Deininger P. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res. 2008;18(3):343–358.
    1. Belinsky SA, Snow SS, Nikula KJ, Finch GL, Tellez CS, Palmisano WA. Aberrant CpG island methylation of the p16INK4a and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. Carcinogenesis. 2002;23(2):335–339.
    1. Bell B, Rose C, Damon A. The Normative Aging Study: an interdisciplinary and longitudinal study of health and aging. Aging Hum Dev. 1972;3:4–17.
    1. Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D, et al. Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res. 2007;67(3):876–880.
    1. Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H, et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev. 2009;130(4):234–239.
    1. Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009;180(5):462–467.
    1. Brook RD, Rajagopalan S, Pope CA, III, Brook JR, Bhatnagar A, Diez-Roux AV, et al. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331–2378.
    1. Castro R, Rivera I, Struys EA, Jansen EEW, Ravasco P, Camilo ME, et al. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem. 2003;49(8):1292–1296.
    1. Chahine T, Baccarelli A, Litonjua A, Wright RO, Suh H, Gold DR, et al. Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort. Environ Health Perspect. 2007;115:1617–1622.
    1. Chen H, Li S, Liu J, Diwan BA, Barrett JC, Waalkes MP. Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis. Carcinogenesis. 2004;25(9):1779–1786.
    1. Dubowsky SD, Suh H, Schwartz J, Coull BA, Gold DR. Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation. Environ Health Perspect. 2006;114:992–998.
    1. Ferris B.G. Epidemiology standardization project (American Thoracic Society). Am Rev Respir Dis. 1978;118(6):1–120.
    1. Fornage M. Unraveling hypertension: epigenomics comes of age. Pharmacogenomics. 2007;8(2):125–128.
    1. Hagan CR, Rudin CM. Mobile genetic element activation and genotoxic cancer therapy: potential clinical implications. Am J Pharmacogenomics. 2002;2(1):25–35.
    1. Han JS, Boeke JD. LINE-1 retrotransposons: modulators of quantity and quality of mammalian gene expression? BioEssays. 2005;27(8):775–784.
    1. Hitchler MJ, Domann FE. Metabolic defects provide a spark for the epigenetic switch in cancer. Free Radic Biol Med. 2009;47(2):115–127.
    1. Janssen NA, Schwartz J, Zanobetti A, Suh HH. Air conditioning and source-specific particles as modifiers of the effect of PM10 on hospital admissions for heart and lung disease. Environ Health Perspect. 2002;110:43–49.
    1. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8(4):253–262.
    1. Kazazian HH, Jr, Moran JV. The impact of L1 retrotransposons on the human genome. Nat Genet. 1998;19(1):19–24.
    1. Koutrakis P, Suh HH, Sarnat JA, Brown KW, Coull BA, Schwartz J.2005Characterization of particulate and gas exposures of sensitive subpopulations living in Baltimore and Boston. Res Rep Health Eff Inst (1311–65.
    1. Laden F, Schwartz J, Speizer FE, Dockery DW. Reduction in fine particulate air pollution and mortality: extended follow-up of the Harvard Six Cities study. Am J Respir Crit Care Med. 2006;173(6):667–672.
    1. Lertratanangkoon K, Wu CJ, Savaraj N, Thomas ML. Alterations of DNA methylation by glutathione depletion. Cancer Lett. 1997;120(2):149–156.
    1. Li T, Schmid CW. Differential stress induction of individual Alu loci: implications for transcription and retrotransposition. Gene. 2001;276(1–2):135–141.
    1. Madrigano J, Baccarelli A, Wright RO, Suh H, Sparrow D, Vokonas PS, et al. Air pollution, obesity, genes and cellular adhesion molecules. Occup Environ Med. 2010;67(5):312–317.
    1. Medina-Ramon M, Schwartz J. Who is more vulnerable to die from ozone air pollution? Epidemiology. 2008;19(5):672–679.
    1. Neidhart M, Rethage J, Kuchen S, Kunzler P, Crowl RM, Billingham ME, et al. Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression. Arthritis Rheum. 2000;43(12):2634–2647.
    1. O’Neill MS, Veves A, Sarnat JA, Zanobetti A, Gold DR, Economides PA, et al. Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occup Environ Med. 2007;64(6):373–379.
    1. Ostertag EM, Kazazian HH., Jr Biology of mammalian L1 retrotransposons. Annu Rev Genet. 2001;35(1):501–538.
    1. Park SK, O’Neill MS, Vokonas PS, Sparrow D, Schwartz J. Effects of air pollution on heart rate variability: the VA Normative Aging Study. Environ Health Perspect. 2005;113:304–309.
    1. Park SK, O’Neill MS, Wright RO, Hu H, Vokonas PS, Sparrow D, et al. HFE genotype, particulate air pollution, and heart rate variability: a gene-environment interaction. Circulation. 2006;114(25):2798–2805.
    1. Puett RC, Hart JE, Yanosky JD, Paciorek C, Schwartz J, Suh H, et al. Chronic fine and coarse particulate exposure, mortality, and coronary heart disease in the Nurses’ Health Study. Environ Health Perspect. 2009;117:1697–1701.
    1. Sarnat JA, Brown KW, Bartell SM, Sarnat SE, Wheeler AJ, Suh HH, et al. The relationship between averaged sulfate exposures and concentrations: results from exposure assessment panel studies in four U.S. cities. Environ Sci Technol. 2009;43(13):5028–5034.
    1. Sarnat JA, Brown KW, Schwartz J, Coull BA, Koutrakis P. Ambient gas concentrations and personal particulate matter exposures: implications for studying the health effects of particles. Epidemiology. 2005;16(3):385–395.
    1. Schulz WA, Steinhoff C, Florl AR. Methylation of endogenous human retroelements in health and disease. Curr Top Microbiol Immunol. 2006;310:211–250.
    1. Schwartz J. The distributed lag between air pollution and daily deaths. Epidemiology. 2000;11(3):320–326.
    1. Schwartz J, Coull B, Laden F, Ryan L. The effect of dose and timing of dose on the association between airborne particles and survival. Environ Health Perspect. 2008;116:64–69.
    1. Schwartz J, Park SK, O’Neill MS, Vokonas PS, Sparrow D, Weiss S, et al. Glutathione-S-transferase M1, obesity, statins, and autonomic effects of particles: gene-by-drug-by-environment interaction. Am J Respir Crit Care Med. 2005;172(12):1529–1533.
    1. Seemayer CA, Distler O, Kuchen S, Muller-Ladner U, Michel BA, Neidhart M, et al. Rheumatoid arthritis: new developments in the pathogenesis with special reference to synovial fibroblasts. Z Rheumatol. 2001;60(5):309–318. [in German]
    1. Suh H, Allen G, Kou P, Burton R. Spatial variation in acidic sulfate and ammonia concentrations within metropolitan Philadelphia. J Air Waste Manag Assoc. 1995;45:442–452.
    1. Szyf M. The dynamic epigenome and its implications in toxicology. Toxicol Sci. 2007;100(1):7–23.
    1. Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B, et al. Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect. 2009;117:217–222.
    1. Wierda RJ, Geutskens SB, Jukema JW, Quax PH, van den Elsen PJ. Epigenetics in atherosclerosis and inflammation. J Cell Mol Med. 2010;14(6A):1225–1240.
    1. Wilson AS, Power BE, Molloy PL. 2007. DNA hypomethylation and human diseases. Biochim Biophys Acta. 1775;(1):138–162.
    1. Yang AS, Estecio MRH, Doshi K, Kondo Y, Tajara EH, Issa JJ. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res. 2004;32(3):e38.
    1. Zanobetti A, Schwartz J. Air pollution and emergency admissions in Boston, MA. J Epidemiol Community Health. 2006;60(10):890–895.
    1. Zanobetti A, Schwartz J. Temperature and mortality in nine US cities. Epidemiology. 2008;19(4):563–570.
    1. Zanobetti A, Schwartz J, Samoli E, Gryparis A, Touloumi G, Atkinson R, et al. The temporal pattern of mortality responses to air pollution: a multicity assessment of mortality displacement. Epidemiology. 2002;13(1):87–93.
    1. Zeger SL, Thomas D, Dominici F, Samet JM, Schwartz J, Dockery D, et al. Exposure measurement error in time-series studies of air pollution: concepts and consequences. Environ Health Perspect. 2000;108:419–426.
    1. Zhu ZZ, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L, et al. 2010Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemioldoi:[Online 15 September 2010]10.1093/ije/dyq154

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj