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Changes in DNA methylation over the growing season differ between North Carolina farmworkers and non-farmworkers

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Abstract

Purpose

The occupational risk to farmworkers, particularly chronic exposure to pesticides, is an acknowledged environmental and work-related health problem. Epigenetics has recently been shown to contribute to a number of complex diseases and traits, including measures of cognitive function and preclinical neurodegenerative disease. We sought to determine whether changes in DNA methylation existed between farmworker and non-farmworker populations and to identify the genes most likely involved in those changes.

Methods

Eighty-three farmworkers and 60 non-farmworkers were selected from PACE4, a community-based, participatory research project comparing occupational exposures between immigrant Latino farmworker and non-farmworker manual workers. Measurements of DNA methylation were performed with the Infinium HumanMethylation450 BeadChip, at the beginning and end of the 2012 growing season. Bonferroni adjustment was used to identify significant findings (p = 1.03 × 10−7, based on 485,000 tested methylation sites), although less stringent criteria (i.e., p ≤ 1 × 10−6) were used to identify sites of interest. Expression quantitative trait locus (eQTL) databases were used to help identify the most likely functional genes for each associated methylation site.

Results

Methylation at 36 CpG sites, located in or near 72 genes, differed between the two groups (p ≤ 1 × 10−6). The difference between the two groups was generally due to an increase in methylation in the farmworkers and a slight decrease in methylation in the non-farmworkers. Enrichment was observed in several biological pathways, including those involved in the immune response, as well as growth hormone signaling, role of BRCA1 in DNA damage response, p70S6K signaling, and PI3K signaling in B lymphocytes.

Conclusions

We identified considerable changes in DNA methylation at 36 CpG sites over the growing season that differed between farmworkers and non-farmworkers. Dominant pathways included immune-related (HLA) processes, as well as a number of diverse biological systems. Further studies are necessary to determine which exposures or behaviors are responsible for the observed changes, and whether these changes eventually lead to disease-related phenotypes in this population.

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References

  • Alavanja MC, Hoppin JA, Kamel F (2004) Health effects of chronic pesticide exposure: cancer and neurotoxicity. Annu Rev Public Health 25:155–197

    Article  Google Scholar 

  • Androutsopoulos VP, Kanavouras K, Tsatsakis AM (2011) Role of paraoxonase 1 (PON1) in organophosphate metabolism: implications in neurodegenerative diseases. Toxicol Appl Pharmacol 256:418–424

    Article  CAS  Google Scholar 

  • Arcury TA, Quandt SA (2003) Pesticides at work and at home: exposure of migrant farmworkers. Lancet 362:2021

    Article  Google Scholar 

  • Arcury TA, Vallejos QM, Marin AJ, Feldman SR, Smith G, Quandt SA (2006) Latino farmworker perceptions of the risk factors for occupational skin disease. Am J Ind Med 49:434–442

    Article  Google Scholar 

  • Arcury TA, Nguyen HT, Summers P, Talton JW, Holbrook LC, Walker FO, Chen H, Howard TD, Galvan L, Quandt SA (2014) Lifetime and current pesticide exposure among Latino farmworkers in comparison to other Latino immigrants. Am J Ind Med 57:776–787

    Article  Google Scholar 

  • Barrett RM, Wood MA (2008) Beyond transcription factors: the role of chromatin modifying enzymes in regulating transcription required for memory. Learn Mem 15:460–467

    Article  CAS  Google Scholar 

  • Calvert GM, Karnik J, Mehler L, Beckman J, Morrissey B, Sievert J, Barrett R, Lackovic M, Mabee L, Schwartz A, Mitchell Y, Moraga-McHaley S (2008) Acute pesticide poisoning among agricultural workers in the United States, 1998-2005. Am J Ind Med 51:883–898

    Article  Google Scholar 

  • Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B (2015) Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci 9:124

    Article  Google Scholar 

  • Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC (2005) Biologic monitoring to characterize organophosphorus pesticide exposure among children and workers: an analysis of recent studies in Washington State. Environ Health Perspect 113:1651–1657

    Article  CAS  Google Scholar 

  • Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60

    Article  CAS  Google Scholar 

  • Guidotti A, Auta J, Davis JM, Dong E, Gavin DP, Grayson DR, Sharma RP, Smith RC, Tueting P, Zhubi A (2014) Toward the identification of peripheral epigenetic biomarkers of schizophrenia. J Neurogenet 28:41–52

    Article  CAS  Google Scholar 

  • Hoppin JA, Umbach DM, London SJ, Alavanja MC, Sandler DP (2002) Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study. Am J Respir Crit Care Med 165:683–689

    Article  Google Scholar 

  • Howard TD, Hsu FC, Grzywacz JG, Chen H, Quandt SA, Vallejos QM, Whalley LE, Cui W, Padilla S, Arcury TA (2010) Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE. Environ Health Perspect 118:1395–1399

    Article  CAS  Google Scholar 

  • Kamel F, Hoppin JA (2004) Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect 112:950–958

    Article  CAS  Google Scholar 

  • Kim KY, Kim DS, Lee SK, Lee IK, Kang JH, Chang YS, Jacobs DR, Steffes M, Lee DH (2010) Association of low-dose exposure to persistent organic pollutants with global DNA hypomethylation in healthy Koreans. Environ Health Perspect 118:370–374

    Article  CAS  Google Scholar 

  • McCauley LA, Anger WK, Keifer M, Langley R, Robson MG, Rohlman D (2006) Studying health outcomes in farmworker populations exposed to pesticides. Environ Health Perspect 114:953–960

    Article  CAS  Google Scholar 

  • Mills PK, Yang R (2003) Prostate cancer risk in California farm workers. J Occup Environ Med 45:249–258

    Article  Google Scholar 

  • Morris TJ, Butcher LM, Feber A, Teschendorff AE, Chakravarthy AR, Wojdacz TK, Beck S (2014) ChAMP: 450 k chip analysis methylation pipeline. Bioinformatics 30:428–430

    Article  CAS  Google Scholar 

  • Na KS, Chang HS, Won E, Han KM, Choi S, Tae WS, Yoon HK, Kim YK, Joe SH, Jung IK, Lee MS, Ham BJ (2014) Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLoS ONE 9:e85425

    Article  Google Scholar 

  • Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, Cota P, Wittnam JL, Gogol-Doering A, Opitz L, Salinas-Riester G, Dettenhofer M, Kang H, Farinelli L, Chen W, Fischer A (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328:753–756

    Article  CAS  Google Scholar 

  • Quandt SA, Hernandez-Valero MA, Grzywacz JG, Hovey JD, Gonzales M, Arcury TA (2006) Workplace, household, and personal predictors of pesticide exposure for farmworkers. Environ Health Perspect 114:943–952

    Article  CAS  Google Scholar 

  • Ray DE (1998) Chronic effects of low level exposure to anticholinesterases–a mechanistic review. Toxicol Lett 102–103:527–533

    Article  Google Scholar 

  • Ray DE, Richards PG (2001) The potential for toxic effects of chronic, low-dose exposure to organophosphates. Toxicol Lett 120:343–351

    Article  CAS  Google Scholar 

  • Reeves M, Schafer KS (2003) Greater risks, fewer rights: U.S. farmworkers and pesticides. Int J Occup Environ Health 9:30–39

    Article  Google Scholar 

  • Shutoh Y, Takeda M, Ohtsuka R, Haishima A, Yamaguchi S, Fujie H, Komatsu Y, Maita K, Harada T (2009) Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats: implication of hormesis-like effects. J Toxicol Sci 34:469–482

    Article  CAS  Google Scholar 

  • Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, Beck S (2013) A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics 29:189–196

    Article  CAS  Google Scholar 

  • Thaler L, Gauvin L, Joober R, Groleau P, de Guzman R, Ambalavanan A, Israel M, Wilson S, Steiger H (2014) Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry 54:43–49

    Article  CAS  Google Scholar 

  • Walton E, Liu J, Hass J, White T, Scholz M, Roessner V, Gollub R, Calhoun VD, Ehrlich S (2014) MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls. Epigenetics 9:1101–1107

    Article  Google Scholar 

  • Wang Y, Fang Y, Zhang F, Xu M, Zhang J, Yan J, Ju W, Brown WT, Zhong N (2014) Hypermethylation of the enolase gene (ENO2) in autism. Eur J Pediatr 173:1233–1244

    Article  CAS  Google Scholar 

  • Westra HJ, Peters MJ, Esko T, Yaghootkar H, Schurmann C, Kettunen J, Christiansen MW, Fairfax BP, Schramm K, Powell JE, Zhernakova A, Zhernakova DV, Veldink JH, Van den Berg LH, Karjalainen J, Withoff S, Uitterlinden AG, Hofman A, Rivadeneira F, ‘t Hoen PA, Reinmaa E, Fischer K, Nelis M, Milani L, Melzer D, Ferrucci L, Singleton AB, Hernandez DG, Nalls MA, Homuth G, Nauck M, Radke D, Volker U, Perola M, Salomaa V, Brody J, Suchy-Dicey A, Gharib SA, Enquobahrie DA, Lumley T, Montgomery GW, Makino S, Prokisch H, Herder C, Roden M, Grallert H, Meitinger T, Strauch K, Li Y, Jansen RC, Visscher PM, Knight JC, Psaty BM, Ripatti S, Teumer A, Frayling TM, Metspalu A, van Meurs JB, Franke L (2013) Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat Genet 45:1238–1243

    Article  CAS  Google Scholar 

  • Xia C, Wang M, Liang Q, Yun L, Kang H, Fan L, Wang D, Zhang G (2014) Changes in monoclonal HLA-DR antigen expression in acute organophosphorus pesticide-poisoned patients. Exp Ther Med 7:137–140

    CAS  Google Scholar 

  • Yehuda R, Flory JD, Bierer LM, Henn-Haase C, Lehrner A, Desarnaud F, Makotkine I, Daskalakis NP, Marmar CR, Meaney MJ (2014) Lower methylation of glucocorticoid receptor gene promoter 1 in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry 77:356–364

    Article  Google Scholar 

  • Yu L, Chibnik LB, Srivastava GP, Pochet N, Yang J, Xu J, Kozubek J, Obholzer N, Leurgans SE, Schneider JA, Meissner A, De Jager PL, Bennett DA (2015) Association of brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease. JAMA Neurol 72:15–24

    Article  Google Scholar 

  • Zhang X, Wallace AD, Du P, Kibbe WA, Jafari N, Xie H, Lin S, Baccarelli A, Soares MB, Hou L (2012) DNA methylation alterations in response to pesticide exposure in vitro. Environ Mol Mutagen 53:542–549

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by NIEHS Grant R01 ES008739.

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Authors and Affiliations

  1. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Timothy D. Howard

  2. Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Fang-Chi Hsu, Haiying Chen & Jennifer W. Talton

  3. Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Sara A. Quandt

  4. Department of Family and Community Medicine, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Phillip Summers & Thomas A. Arcury

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  1. Timothy D. Howard
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  2. Fang-Chi Hsu
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  3. Haiying Chen
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  4. Sara A. Quandt
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Correspondence to Timothy D. Howard.

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Howard, T.D., Hsu, FC., Chen, H. et al. Changes in DNA methylation over the growing season differ between North Carolina farmworkers and non-farmworkers. Int Arch Occup Environ Health 89, 1103–1110 (2016). https://doi.org/10.1007/s00420-016-1148-0

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  • DOI: https://doi.org/10.1007/s00420-016-1148-0

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