Environmental Science and Pollution Research

, Volume 25, Issue 12, pp 11981–11986 | Cite as

Modulatory role of GSTT1 and GSTM1 in Punjabi agricultural workers exposed to pesticides

Research Article


Glutathione S-transferases are important detoxification enzymes involved in the metabolism of endogenous as well as exogenous compounds. Individuals differ in metabolic capacity due to inherited genetic variations. Due to the polymorphism exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the present study was aimed towards the determination of the frequency distribution of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to investigate their contribution in susceptibility to increased disease risk. A total of 513 subjects were included in this study, out of which 250 were agriculture workers and 263 were non-exposed occupationally. GSTT1 and GSTM1 null-genotype distribution was analyzed through multiplex-PCR method. Complete gene deletion in either of the genes was strongly associated with an increased risk (OR = 1.8; 95% CI = 1.3–2.6; p < 0.0008) of DNA/cytogenetic damage, cancer, infertility, and many other serious health effects. Therefore, homozygous deletion in GSTT1 or GSTM1 could play a modulatory role in health of workers with long-term exposure to pesticides.


Glutathione S-transferases GSTT1 GSTM1 Xenobiotics Pesticides Agriculture 


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Research involving human participants

The study has been approved by the Ethics Committee of Guru Nanak Dev University, Amritsar.

Informed consent

Informed consent was taken before all the investigations.


  1. Adeli K, Ogbonna G (1990) Rapid purification of human DNA from whole blood for potential application in clinical chemistry laboratories. Clin Chem 36(2):261–264Google Scholar
  2. Alif SM, Dharmage SC, Benke G, Dennekamp M, Burgess JA, Perret JL, Lodge CJ, Morrison S, Johns DP, Giles GG, Gurrin LC, Thomas PS, Hopper JL, Vermeulen R, Kromhout H, Walters EH, Abramson MJ, Matherson MC (2017) Occupational exposure to pesticides are associated with fixed airflow obstruction in middle-age. Thorax 72(11):990–997. CrossRefGoogle Scholar
  3. Amr S, Dawson R, Saleh DA, Magder LS, St. George DM, El-Daly M, Squibb K, Mikhail NN, Abdel-Hamid M, Khaled H, Loffredo CA (2015) Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers. Arch Environ Occup Health 70(1):19–26. CrossRefGoogle Scholar
  4. Arand M, Muhlbauer R, Hengstler J, Jager E, Fuchs J, Winkler L, Oesch F (1996) A multiplex polymerase chain reaction protocol for the simultaneous analysis of glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem 236(1):184–186. CrossRefGoogle Scholar
  5. Baldi I, Robert C, Piantoni F, Tual S, Bouvier G, Lebailly P, Raherison C (2014) Agricultural exposure and asthma risk in the AGRICAN French cohort. Int J Hyg Environ Health 217(4–5):435–442. CrossRefGoogle Scholar
  6. Bonner MR, Freeman LEB, Hoppin JA, Koutros S, Sandler DP, Lynch CF, Hines CJ, Thomas K, Blair A, Alavanja MCR (2017) Occupational exposure to pesticides and the incidence of lung cancer in the agricultural health study. Environ Health Perspect 125(4):544–551Google Scholar
  7. Brisson GD, Alves LR, Pombo-de-Oliveira MS (2015) Genetic susceptibility in childhood acute leukaemias: a systematic review. Ecancer 9:539CrossRefGoogle Scholar
  8. Buzio L, Palma GD, Mozzoni P, Tondel M, Buzio C, Franchini I, Axlson O, Mutti A (2003) Glutathione S-transferase M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals. Occup Environ Med 60(10):789–793. CrossRefGoogle Scholar
  9. Coles B, Ketterer B (1990) The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit Rev Biochem Mol Biol 25(1):47–70. CrossRefGoogle Scholar
  10. Costa C, Teixeira JP, Silva S, Torres JR, Coelho P, Gaspar J, Alves M, Laffon B, Rueff J, Mayan O (2006) Cytogenetic and molecular biomonitoring of a Portuguese population exposed to pesticides. Mutagenesis 21(5):343–350. CrossRefGoogle Scholar
  11. DaSilva FR, Da Silva J, Allgayer MC, Simon CF, Dias JF, Santos CEI, Salvador M, Branco C, Schneider NB, Kahl V, Rohr P, Kvitko V (2012) Genotoxic biomonitoring of tobacco farmers: biomarkers of exposure, of early biological effects of susceptibility. J Hazard Mater 225-226:81–90. CrossRefGoogle Scholar
  12. Directorate of Agriculture, Government of Punjab (2017a) Introduction to Punjab. National Informatics centre, Punjab State Centre, Chandigarh. Google Scholar
  13. Directorate of Agriculture, Government of Punjab (2017b) Classification of Area. National Informatics centre, Punjab State Centre, Chandigarh. Google Scholar
  14. Directorate of Agriculture, Government of Punjab (2017c) Consumption of insecticides. National Informatics centre, Punjab State Centre, Chandigarh. Google Scholar
  15. Farr SL, Cooper GS, Cai J, Savitz DA, Sandler DP (2004) Pesticide use and menstrual cycle characteristics among premenopausal women in the agricultural health study. Am J Epidemiol 160(12):1194–1204. CrossRefGoogle Scholar
  16. Firozi PF, Bondy ML, Sahin AA, Chang P, Lukmanji F, Singletary ES, Hassan MM, Li D (2002) Aromatic DNA adducts and polymor-phisms of CYP1A1, NAT2, and GSTM1 in breast cancer. Carcinogenesis 23(2):301–306. CrossRefGoogle Scholar
  17. Franco FC, Alves AA, Godoy FR, Avelar JB, Rodrigues DD, Pedroso TMA, deCruz AD, Nomura F, eSilva DM (2016) Evaluating genotoxic risks in Brazilian public health agents occupationally exposed to pesticides: a multi-biomarker approach. Environ Sci Pollut Res 23(19):19723–19734. CrossRefGoogle Scholar
  18. Godoy FR, Costa EOA, Reis AAS, Batista MP, Melo AV, Goncalves MW, Cruz AS, Melo COA, Minasi LB, Ribeiro CL, da Cruz AD, de Melo E Silva D (2014) Do GSTT1 and GSTM1 polymorphisms influence intoxication events in individuals occupationally exposed to pesticides? Environ Sci Pollut Res 21(5):3706–3712. CrossRefGoogle Scholar
  19. Hamouda OS, Perrin J, Archard V, Courbiere B, Grillo JM, Sari-Minodier I (2015) Association between sperm abnormalities and occupational environment among male consulting for couple infertility. J Gynecol Obstet Biol Reprod (Paris) 45(1):1–10CrossRefGoogle Scholar
  20. Hernandez AF, Lazasana M, Gil F, Rodriguez-Barranco M, Pla A, Lopez-Guardino O (2012) Evaluation of pesticide induced oxidative stress from a gene-environment interaction perspective. Toxicology 307:95–102CrossRefGoogle Scholar
  21. Hernandez AF, Gil F, Lacassana M, Barranco MR, Tsatsakis AM, Requena M, Parron T and Alarcon R (2013) Pesticide exposure and genetic variation in xenobiotic metabolizing enzymes interact to induce biochemical liver damage. Food Chem Toxicol 61:144–151. CrossRefGoogle Scholar
  22. Hodgson E (2012) Introduction to pesticide niotransformation and disposition. In: Pesticide biotransformation and disposition. Elsevier Inc. 2012 pp1–3Google Scholar
  23. Hung RJ, Boffetta P, Brennan P, Malavielle C, Hautefeuille A, Donato F, Gelatti U, Spaliviero M, Placidi D, Carta A, diCarlo AS, Porru S (2004) GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population. Int J Cancer 110(4):598–604. CrossRefGoogle Scholar
  24. Jiang S, Yu L, Cheng J, Leng S, Dai Y, Zhang Y, Niu Y, Yan H, Qu W, Zhang C, Zhang K, Yang R, Zhou L, Zheng Y (2010) Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde. Mutat Res Genet Toxicol Environ Mutagen 695(2010):9–15. CrossRefGoogle Scholar
  25. Jiang Z, Liang K, Zhang Q, Tao L (2012) Glutathione S-transferases polymorphisms confer susceptibility to senile cortical cataract in the Han Chinese population. Mol Vis 18:1247–1252Google Scholar
  26. Karami S, Boffetta P, Rothman N, Hung RJ, Stewart T, Zaridze D, Navritalova M, Mates D, Janout V, Kollarova H, Bencko V, Szeszenia-Dabrowska N, Holcatova I, Mukeria A, Gromiec J, Chanock SJ, Brennan P, Chow WH, Moore LF (2008) Renal cell cacrcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms. Carcinogenesis 29(8):1567–1571. CrossRefGoogle Scholar
  27. Martenies SE, Perry MJ (2013) Environmental and occupational pesticide exposure and human sperm parameters: a systematic review. Toxicology 307:66–73. CrossRefGoogle Scholar
  28. Online Mendelian Inheritance in Man, OMIM (2017) McKusick-Nathans Institute of Genetics Medicine, Johns Hopkins University (Baltimore, MD). Accessed 15 Dec 2017
  29. Pinhel MAS, Sado CL, Longo GS, Gregorio ML, Amorim GS, Florim GMS, Mazeti CM, Martins DP, Oliveira FN, Nakazone MA, Tognola WA, Souza DRS (2013) Nullity of GSTT1/GSTM1 related to pesticides is associated with Parkinson’s disease. Arq Neuropsiquiatr 71(8):527–532. CrossRefGoogle Scholar
  30. Quandt SA, Walker FO, Talton JW, Summers P, Chen H, McLeod DK, Arcury TA (2016) Olfactory function in Latino farmworkers: subclinical neurological effects of pesticide exposure in a vulnerable population. J Occup Environ Med 58(3):248–253. CrossRefGoogle Scholar
  31. Rubes J, Rybar R, Prinosilova P, Veznik Z, Chvatalova I, Solansky I, Sram RJ (2010) Genetic polymorphisms influence the susceptibility of men to sperm DNA damage associated with exposure to air pollution. Mutat Res 683(1-2):9–15. CrossRefGoogle Scholar
  32. Safarinejad MR, Shafiei N, Safarinejad S (2010) The association of glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) with idiopathic male infertility. J Hum Genet 55(9):565–570. CrossRefGoogle Scholar
  33. Sasaki S, Kondo T, Sata F, Saijo Y, Katoh S, Nakajima S, Ishizuka M, Fujita S and Kishi R (2006) Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects. Mol Hum Reprod 12(2):77–83. CrossRefGoogle Scholar
  34. Sharma E, Mustafa M, Pathak R, Guleria K, Ahmed RS, Vaid NB, Banerjee BD (2012) A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides. Eur J Obstet Gynecol Reprod Biol 161(2012):163–169. CrossRefGoogle Scholar
  35. Silva JFS, Mattos IE, Luz LL, Carmo CN, Aydos RD (2016) Exposure to pesticides and prostate cancer: systematic review of the literature. Rev Environ Health 31(3):311–327. CrossRefGoogle Scholar
  36. Singh S, Kumar V, Singh P, Thakur S, Banerjee BD, Rautela RS, Grover SS, Rawat DS, Pasha ST, Jain SK, Rai A (2011) Genetic polymorphism of GSTM1, GSTT1 and GSTP1 and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides. Mut Res 725(1–2):36–42. CrossRefGoogle Scholar
  37. Singh S, Kumar V, Singh P, Banerjee BD, Rautela RS, Grover SS, Rawat DS, Pasha ST, Jain SK, Rai A (2012) Influence of CYP2C9, GSTM1, GSTT1 and NAT2 genetic polymorphisms on DNA damage in workers occupationally exposed to organophosphate pesticides. Mut Res 741(1–2):101–108. CrossRefGoogle Scholar
  38. Steenland K, Jenkins B, Ames RG, O'Malley M, Chrislip D and Russo J (1994) Chronic neurological sequelae to organo-phosphate pesticide poisoning. Am J Public Health 84(5):731–736. CrossRefGoogle Scholar
  39. Swan SH, Kruse RL, Liu F, Barr DB, Drobnis EZ, Redmon JB, Wang C, Brazil C, Overstreet JW, the study for Future Families Research Group (2003) Semen quality in relation to biomarkers of pesticide exposure. Environ Health Perspect 111(12):1478–1484CrossRefGoogle Scholar
  40. Zhang X, Wu M, Yao H, Yang Y, Cui M, Tu Z, Stallones L, Xiang H (2016) Pesticide poisoning and neurobehavioral function among farm workers in Jiangsu, People’s republic of China. Cortex 74:396–404. CrossRefGoogle Scholar
  41. Zheng Y, Ni XJY, Shen F, Jiang H, Wang M, Hu G, Tao S (2016) Genetic polymor-phisms of glutathione S-transferase (GSTM1, GSTT1 and GSTP1) with esophageal cancer risk: a meta-analysis. Int J Clin Exp Med 9(7):13268–13280Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Human GeneticsGuru Nanak Dev UniversityAmritsarIndia

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