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Association of intronic polymorphisms (rs1549339, rs13402242) and mRNA expression variations in PSMD1 gene in arsenic-exposed workers

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Abstract

Ubiquitin-proteasome system (UPS) gene, PSMD1, is an important gene for neutralization of damaged and misfolded protein(s). The current study was designed to study the genetic and expression variations of PSMD1 gene as a consequence of arsenic exposure and its potential implications in arsenic induced diseases. In the present study, 250 blood samples of exposed industrial workers along with 250 controls were used. Initially, tetra amplification refractory mutation system-PCR was used to determine the role of PSMD1 gene polymorphisms (rs1549339, rs13402242) in industrial workers and controls. Frequency of homozygous mutant genotype of rs1549339 (OR: 2.23, 95% CI: 1.51–3.32, p = 0.0001) and rs13402242 (OR: 2.96, 95% CI: 1.52–5.75, p = 0.001) was observed significantly higher in exposed individuals vs controls. Secondly, qPCR was performed for expression analysis of PSMD1 gene. Significant down-regulated expression of PSMD1 gene (p < 0.0001) was observed vs controls, and this down-regulation was observed more pronounced in smokers (p < 0.0001) with maximum exposure duration (p < 0.0008). This down-regulated expression was observed significantly more pronounced in welding (p < 0.004) and brick kiln industries (p < 0.04) compared to other selected industries. The obtained results suggest that the exposure to arsenic may have an increased risk of developing disease(s) because of arsenic-induced PSMD1 variations.

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References

  • Alsmadi O, Muiya P, Khalak H, Al-Saud H, Meyer BF, Al-Mohanna F, Alshahid M, Dzimiri N (2009) Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. Ann Hum Genet 73:475–483

    Article  CAS  Google Scholar 

  • Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL (2004) Urinary creatinine concentrations in the US population: implications for urinary biologic monitoring measurements. Environ Health Perspect 113(2):192–200

    Article  CAS  Google Scholar 

  • Bennett DA, Xu P, Clarke R, Zondervan K, Parish S, Palmer A, Cardon L, Peto R, Lathrop M, Collins R (2008) The exon 1–8C/G SNP in the PSMA6 gene contributes only a small amount to the burden of myocardial infarction in 6946 cases and 2720 controls from a United Kingdom population. Eur J Hum Genet 16:480

    Article  CAS  Google Scholar 

  • Bibi Z, Khan ZI, Ahmad K, Ashraf M, Hussain A, Nudrat AA (2014) Vegetables as a potential source of metals and metalloids for human nutrition: a case study of Momordica charantia grown in soil irrigated with domestic sewage water in Sargodha, Pakistan. Pak J Zool 46(3)

  • Chamba P, Nunes E (2016) Work-related asthma among workers in the wood-processing industry: a review: allergies in the workplace. Curr Allergy Clin Immunol 29:110–117

    Google Scholar 

  • Cheng J, Leng S, Dai Y, Huang C, Pan Z, Niu Y, Li B, Zheng Y (2007) Association between nucleotide excision repair gene polymorphisms and chromosomal damage in coke-oven workers. Biomarkers. 12(1):76–86

    Article  CAS  Google Scholar 

  • da Fonseca PC, Morris EP (2008) Structure of the human 26S proteasome subunit radial displacements open the gate into the proteolytic core. J Biol Chem 283:23305–23314

    Article  CAS  Google Scholar 

  • Deshaies RJ (2014) Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy. BMC Biol 12:94

    Article  CAS  Google Scholar 

  • Eaton DL, Klaassen CD (2001) Casarett and Doull’s Toxicology: The basic science of poisons. New York. 11–34

  • Faita F, Cori L, Bianchi F, Andreassi M (2013) Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies. Int J Environ Res Public Health 10:1527–1546

    Article  CAS  Google Scholar 

  • Fortunato G, Marciano E, Zarrilli F, Mazzaccara C, Intrieri M, Calcagno G, Vitale DF, La Manna P, Saulino C, Marcelli V, Sacchetti L (2004) Paraoxonase and superoxide dismutase gene polymorphisms and noise-induced hearing loss. Clin Chem 50(11):2012–2018

    Article  CAS  Google Scholar 

  • Gamble MV, Liu X, Ahsan H, Pilsner JR, Ilievski V, Slavkovich V, Parvez F, Levy D, Factor-Litvak P, Graziano JH (2005) Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect 113(12):1683–1688

    Article  CAS  Google Scholar 

  • Gao M, Li Y, Xue X, Long J, Chen L, Shah W, Kong Y (2014) Impact of AhR, CYP1A1 and GSTM1 genetic polymorphisms on TP53 R273G mutations in individuals exposed to polycyclic aromatic hydrocarbons. Asian Pac J Cancer Prev 15:2699–2705

    Article  Google Scholar 

  • Gomes AV (2013) Genetics of proteasome diseases. Scientifica 2013:1–30

    Article  CAS  Google Scholar 

  • Grashow R, Zhang J, Fang SC, Weisskopf MG, Christiani DC, Kile ML, Cavallari JM (2014) Inverse association between toenail arsenic and body mass index in a population of welders. Environ Res 131:131–133

    Article  CAS  Google Scholar 

  • Grigoreva TA, Tribulovich VG, Garabadzhiu AV, Melino G, Barlev NA (2015) The 26S proteasome is a multifaceted target for anti-cancer therapies. Oncotarget 6:24733

    Article  Google Scholar 

  • Güngör N, Knaapen AM, Munnia A, Peluso M, Haenen GR, Chiu RK, Godschalk RW, van Schooten FJ (2009) Genotoxic effects of neutrophils and hypochlorous acid. Mutagenesis 25:149–154

    Article  CAS  Google Scholar 

  • Güngör N, Pennings JL, Knaapen AM, Chiu RK, Peluso M, Godschalk RW, Van Schooten FJ (2010) Transcriptional profiling of the acute pulmonary inflammatory response induced by LPS: role of neutrophils. Respir Res 11:24

    Article  CAS  Google Scholar 

  • Hall M, Chen Y, Ahsan H, Slavkovich V, Van Geen A, Parvez F, Graziano J (2006) Blood arsenic as a biomarker of arsenic exposure: results from a prospective study. Toxicology. 225(2–3):225–233

    Article  CAS  Google Scholar 

  • Hanna J, Finley D (2007) A proteasome for all occasions. FEBS Lett 581:2854–2861

    Article  CAS  Google Scholar 

  • Hempel S (2013) The inheritor’s powder: a tale of arsenic, murder, and the new forensic science. WW Norton & Company, New York City

    Google Scholar 

  • Hernández A, Xamena N, Surrallés J, Sekaran C, Tokunaga H, Quinteros D, Creus A, Marcos R (2008) Role of the Met287Thr polymorphism in the AS3MT gene on the metabolic arsenic profile. Mutat Res Fundam Mol Mech Mutagen 637:80–92

    Article  CAS  Google Scholar 

  • Ishak I, Rosli FD, Mohamed J, Ismail MF (2015) Comparison of digestion methods for the determination of trace elements and heavy metals in human hair and nails. Malays J Med Sci 22(6):11–20

    Google Scholar 

  • Jonker PK, van Dam GM, Oosting SF, Kruijff S, Fehrmann RS (2017) Identification of novel therapeutic targets in anaplastic thyroid carcinoma using functional genomic mRNA-profiling: paving the way for new avenues? Surgery 161:202–211

    Article  Google Scholar 

  • Khlifi R, Hamza-Chaffai A (2010) Head and neck cancer due to heavy metal exposure via tobacco smoking and professional exposure: a review. Toxicol Appl Pharmacol 248:71–88

    Article  CAS  Google Scholar 

  • Kim YJ, Choi JY, Paek D, Chung HW (2008) Association of the NQO1, MPO, and XRCC1 polymorphisms and chromosome damage among workers at a petroleum refinery. J Toxic Environ Health A 71(5):333–341

    Article  CAS  Google Scholar 

  • Labbadia J, Morimoto RI (2015) The biology of proteostasis in aging and disease. Annu Rev Biochem 84:435–464

    Article  CAS  Google Scholar 

  • Li XT, Li X, Hu FF, Shen HX, Cao JL, Zhong L, Zhang ZD, Zhu BL (2013) Association between paraoxonase 2 gene polymorphisms and noise-induced hearing loss in the Chinese population. J Occup Health 12-0242

  • Liu X, Wang X, Shen Y, Wu L, Ruan X, Lindpaintner K, Yusuf S, Engert JC, Anand S, Tan X (2009) The functional variant rs1048990 in PSMA6 is associated with susceptibility to myocardial infarction in a Chinese population. Atherosclerosis 206:199–203

    Article  CAS  Google Scholar 

  • Liu J, X-j Y, J-x L, L-m T, J-x Q, Liu J, X-h C, Wang Y-f, Z-y S, J-l Z (2012) Validation of the association between PSMA6− 8 C/G polymorphism and type 2 diabetes mellitus in Chinese Dongxiang and Han populations. Diabetes Res Clin Pract 98:295–301

    Article  CAS  Google Scholar 

  • Lomelin D, Jorgenson E, Risch N (2010) Human genetic variation recognizes functional elements in noncoding sequence. Genome Res 20:311–319

    Article  CAS  Google Scholar 

  • Luo L, Li Y, Gao Y, Zhao L, Feng H, Wei W, Qiu C, He Q, Zhang Y, Fu S, Sun D (2018) Association between arsenic metabolism gene polymorphisms and arsenic-induced skin lesions in individuals exposed to high-dose inorganic arsenic in Northwest China. Sci Rep 8(1):413

    Article  CAS  Google Scholar 

  • Ma Y, Chen B, Xu X, Lin G (2013) Prospective nested case–control study of feature genes related to leukemic evolution of myelodysplastic syndrome. Mol Biol Rep 40:469–476

    Article  CAS  Google Scholar 

  • Mahjabeen I, Masood N, Baig RM, Sabir M, Inayat U, Malik FA, Kayani MA (2012) Novel mutations of OGG1 base excision repair pathway gene in laryngeal cancer patients. Familial Cancer 11:587–593

    Article  CAS  Google Scholar 

  • Mahjabeen I, Ali K, Zhou X, Kayani MA (2014) Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma. Tumor Biol 35:5971–5983

    Article  CAS  Google Scholar 

  • Mahmood Q, Wang J, Pervez A, Meryem SS, Waseem M, Ullah Z (2015) Health risk assessment and oxidative stress in workers exposed to welding fumes. Toxicol Environ Chem 97(5):634–639

    Article  CAS  Google Scholar 

  • Mairinger FD, Walter RFH, Theegarten D, Hager T, Vollbrecht C, Christoph DC, Worm K, Ting S, Werner R, Stamatis G (2014) Gene expression analysis of the 26S proteasome subunit PSMB4 reveals significant upregulation, different expression and association with proliferation in human pulmonary neuroendocrine tumours. J Cancer 5:646

    Article  CAS  Google Scholar 

  • Matthews NH, Fitch K, Li WQ, Morris JS, Christiani DC, Qureshi AA, Cho E (2019) Exposure to trace elements and risk of skin cancer: a systematic review of epidemiologic studies. Cancer Epidemiol Prev Biomarkers 28(1):3–21

    Article  Google Scholar 

  • Nakayama T, Kodama M, Nagata C (1984) Generation of hydrogen peroxide and superoxide anion radical from cigarette smoke. GANN Jpn J Cancer Res 75:95–98

    CAS  Google Scholar 

  • Nakayama T, Kaneko M, Kodama M, Nagata C (1985) Cigarette smoke induces DNA single-strand breaks in human cells. Nature 314:462

    Article  CAS  Google Scholar 

  • Pi J, Horiguchi S, Sun Y, Nikaido M, Shimojo N, Hayashi T, Yamauchi H, Itoh K, Yamamoto M, Sun G (2003) A potential mechanism for the impairment of nitric oxide formation caused by prolonged oral exposure to arsenate in rabbits. Free Radic Biol Med 35:102–113

    Article  CAS  Google Scholar 

  • Pickering AM, Davies KJ (2012) Degradation of damaged proteins: the main function of the 20S proteasome. In Progress in molecular biology and translational science (Vol. 109). Academic Press, Cambridge, pp 227–248

  • Priyadarshini UI, Bhaluka V, Prashanth C, Karishna PP, Reddy PP (2018) Association of polymorphisms of GSTM1 and GSTT1 genes with male infertility in steel industry workers. Int J Pure App Biosci 6(3):214–221

    Article  Google Scholar 

  • Qian X, Ding E, Pan L, Tang J, Ouyang Y, Xu M, Zhang H, Zhu B (2018) Association of polymorphisms in the cytochrome P450 gene with susceptibility to lead poisoning in a Chinese population. Int J Clin Exp Med 11(11):12445–12452

    CAS  Google Scholar 

  • Raza M, Mahjabeen I, Fahim M, Malik WA, Khan AU, Kayani MA, Khan A, Akram Z (2018) Redox balance and DNA fragmentation in arsenic-exposed occupational workers from different industries of Pakistan. Environ Sci Pollut Res 25(33):33381–33390

    Article  CAS  Google Scholar 

  • Rekhadevi PV, Mahboob M, Rahman MF, Grover P (2009) Genetic damage in wood dust-exposed workers. Mutagenesis 24:59–65

    Article  CAS  Google Scholar 

  • Rin K, Kawaguchi K, Yamanaka K, Tezuka M, Oku N, Okada S (1995) DNA-strand breaks induced by dimethylarsinic acid, a metabolite of inorganic arsenics, are strongly enhanced by superoxide anion radicals. Biol Pharm Bull 18:45–48

    Article  CAS  Google Scholar 

  • Saeed S, Mahjabeen I, Sarwar R, Bashir K, Kayani MA (2017) Haplotype analysis of XRCC2 gene polymorphisms and association with increased risk of head and neck cancer. Sci Rep 7(1):13210

    Article  CAS  Google Scholar 

  • Sharma B, Singh S, Siddiqi NJ (2014) Biomedical implications of heavy metals induced imbalances in redox systems. Biomed Res Int 2014:1–26

    Google Scholar 

  • Shi H, Shi X, Liu KJ (2004) Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem 255:67–78

    Article  CAS  Google Scholar 

  • Sørensen M, Autrup H, Møller P, Hertel O, Jensen SS, Vinzents P, Knudsen LE, Loft S (2003) Linking exposure to environmental pollutants with biological effects. Mutat Res Rev Mutat Res 544:255–271

    Article  CAS  Google Scholar 

  • Stanhill A, Haynes CM, Zhang Y, Min G, Steele MC, Kalinina J, Martinez E, Pickart CM, Kong X-P, Ron D (2006) An arsenite-inducible 19S regulatory particle-associated protein adapts proteasomes to proteotoxicity. Mol Cell 23:875–885

    Article  CAS  Google Scholar 

  • Stuart PE, Nair RP, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson JE, Li Y, Weidinger S, Eberlein B, Gieger C (2010) Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet 42:1000

    Article  CAS  Google Scholar 

  • Sun H-J, Rathinasabapathi B, Wu B, Luo J, Pu L-P, Ma LQ (2014) Arsenic and selenium toxicity and their interactive effects in humans. Environ Int 69:148–158

    Article  CAS  Google Scholar 

  • Tao N, Ge H, Wu W, An H, Liu J, Xu X (2018) Association of glucocorticoid receptor gene polymorphism and occupational stress with hypertension in desert petroleum workers in Xinjiang, China. BMC Med Genet 19(1):213

    Article  CAS  Google Scholar 

  • Tsvetkov P, Mendillo ML, Zhao J, Carette JE, Merrill PH, Cikes D, Varadarajan M, van Diemen FR, Penninger JM, Goldberg AL (2015) Compromising the 19S proteasome complex protects cells from reduced flux through the proteasome. Elife 4:e08467

    Article  Google Scholar 

  • Vejahati F, Xu Z, Gupta R (2010) Trace elements in coal: associations with coal and minerals and their behavior during coal utilization–a review. Fuel 89:904–911

    Article  CAS  Google Scholar 

  • Wang G-S, Cooper TA (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8:749

    Article  CAS  Google Scholar 

  • Wang J, Maldonado MA (2006) The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell Mol Immunol 3:255–261

    CAS  Google Scholar 

  • Wang M, Wang S, Song Z, Ji X, Zhang Z, Zhou J, Ni C (2001) Associations of IL-4, IL-4R, and IL-13 gene polymorphisms in coal workers’ pneumoconiosis in China: a case-control study. PLoS One 6(8):e22624

    Article  CAS  Google Scholar 

  • Wiseman RL, Chin K-T, Haynes CM, Stanhill A, Xu C-F, Roguev A, Krogan NJ, Neubert TA, Ron D (2009) Thioredoxin-related protein 32 is an arsenite-regulated thiol reductase of the proteasome 19 S particle. J Biol Chem 284:15233–15245

    Article  CAS  Google Scholar 

  • Yun C, Stanhill A, Yang Y, Zhang Y, Haynes CM, Xu C-F, Neubert TA, Mor A, Philips MR, Ron D (2008) Proteasomal adaptation to environmental stress links resistance to proteotoxicity with longevity in Caenorhabditis elegans. Proc Natl Acad Sci 105:7094–7099

    Article  CAS  Google Scholar 

  • Zhang X, Liu Y, Zhang L, Yang Z, Shao Y, Jiang C, Wang Q, Fang X, Xu Y, Wang H, Zhang S (2014) Genetic variations in protocadherin 15 and their interactions with noise exposure associated with noise-induced hearing loss in Chinese population. Environ Res 135:247–252

    Article  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge the financial and infrastructural support from the Higher Education Commission (HEC) and the COMSATS University Islamabad (CUI). The authors are thankful to the industrial workers and control individuals for the blood samples collections.

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Authors and Affiliations

  1. Cancer Genetics & Epigenetics Lab, Department of Biosciences, COMSATS University, Park Road Chak shahzad, Islamabad, Pakistan

    Saqiba Ahmad, Bushra Arif, Zertashia Akram, Malik Waqar Ahmed, Asad Ullah Khan, Mahmood Akhtar Kayani & Ishrat Mahjabeen

  2. National University of Medical Sciences, Rawalpindi, Pakistan

    Muhammad Zahid Hussain

  3. Federal Govt Education Institution, Rawalpindi, Pakistan

    Faisal Rahman

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  1. Saqiba Ahmad
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  2. Bushra Arif
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Correspondence to Ishrat Mahjabeen.

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Ahmad, S., Arif, B., Akram, Z. et al. Association of intronic polymorphisms (rs1549339, rs13402242) and mRNA expression variations in PSMD1 gene in arsenic-exposed workers. Environ Sci Pollut Res 27, 11425–11437 (2020). https://doi.org/10.1007/s11356-019-07422-x

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