Modulatory role of GSTT1 and GSTM1 in Punjabi agricultural workers exposed to pesticides
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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.
KeywordsGlutathione 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 was taken before all the investigations.
- 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
- 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. https://doi.org/10.1136/thoraxjnl-2016-209665 CrossRefGoogle Scholar
- 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. https://doi.org/10.1080/19338244.2013.853646 CrossRefGoogle Scholar
- 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. https://doi.org/10.1006/abio.1996.0153 CrossRefGoogle Scholar
- 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
- 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. https://doi.org/10.1136/oem.60.10.789 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/j.jhazmat.2012.04.074 CrossRefGoogle Scholar
- 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. https://doi.org/10.1007/s11356-016-7179-y CrossRefGoogle Scholar
- 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. https://doi.org/10.1007/s11356-013-2349-7 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/j.fct.2013.05.012 CrossRefGoogle Scholar
- Hodgson E (2012) Introduction to pesticide niotransformation and disposition. In: Pesticide biotransformation and disposition. Elsevier Inc. 2012 pp1–3Google Scholar
- 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. https://doi.org/10.1002/ijc.20157 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/j.mrgentox.2009.09.011 CrossRefGoogle Scholar
- 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
- 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. https://doi.org/10.1093/carcin/bgn153 CrossRefGoogle Scholar
- Online Mendelian Inheritance in Man, OMIM (2017) McKusick-Nathans Institute of Genetics Medicine, Johns Hopkins University (Baltimore, MD). https://omim.org/ Accessed 15 Dec 2017
- 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. https://doi.org/10.1590/0004-282X20130076 CrossRefGoogle Scholar
- 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. https://doi.org/10.1097/JOM.0000000000000672 CrossRefGoogle Scholar
- 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. https://doi.org/10.1093/molehr/gal013 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/j.ejogrb.2012.01.008 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/j.mrgentox.2011.06.006 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/j.mrgentox.2011.11.001 CrossRefGoogle Scholar
- 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