Abstract
Antioxidant enzymes such as glutathione S-transferases (GSTs) and cytochromes P450 (CYPs) are involved in the metabolism and detoxification of cytotoxic compounds, as well as the elimination of reactive oxygen species (ROS). Therefore, alterations in the structure of these enzymes could result in prolonged production of ROS with subsequent risk of development of disorders such as presbycusis. This study aimed to investigate the association between CYP1A1 (rs4646903, rs1048943) and GSTs (GSTM1-deletion, GSTT1-deletion, GSTP1-rs1695) with presbycusis risk in an Iranian population which was followed by an in silico approach. In a case-control study, 280 subjects including 140 cases with presbycusis and 140 healthy controls were enrolled. Genotypes of single-nucleotide polymorphisms (SNPs) were detected by PCR-RFLP method and the genotype of the above mentioned deletions was determined by touchdown PCR. Some bioinformatics tools were employed to evaluate the impact of SNPs on the gene function. SNP analysis revealed that there are significant associations between rs1048943 (AG vs. AA: OR = 2.46, 95%CI = 1.30–4.65, p = 0.006; GG + AG vs. AA: OR = 2.53, 95%CI = 1.36–4.69, p = 0.003; G vs. A: OR = 2.36, 95%CI = 1.33–4.17, p = 0.003) and rs4646903 (C vs. T: OR = 1.45, 95%CI = 1.02–2.06, p = 0.040) variations and increased risk of presbycusis. However, there was no significant association between rs1695 and presbycusis risk. Also, significant associations were observed between GSTM1 (OR = 4.28, 95%CI = 1.18–15.52, p = 0.027) and GSTT1 (OR = 1.64, 95%CI = 1.02–2.65, p = 0.041) deletions and elevated risk of presbycusis. Moreover, the combination analysis revealed a significant association between GSTM1+/GSTT1− genotype and presbycusis susceptibility (OR = 1.63, 95%CI = 1.00–2.67, p = 0.049). In silico analysis revealed that the rs1048943 SNP could influence significantly on the RNA structure of CYP1A1 (distance: 0.1454; p value: 0.1799). Based on our findings, the rs4646903, rs1048943 SNPs as well as GSTM1 and GSTT1 deletions could be considered as genetic risk factors for the development and progression of presbycusis.
Similar content being viewed by others
References
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7:248–249
Ates NA, Ünal M, Tamer L, Derici E, Karakas S, Ercan B, Pata YS, Akbas Y, Vayisoglu Y, Çamdeviren H (2005) Glutathione S-transferase gene polymorphisms in presbycusis. Otology & Neurotology 26:392–397
Bafrani HH, Ahmadi M, Jahantigh D, Karimian M (2019) Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis. J Cell Biochem 120:18020–18030
Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495
Ballenger JJ, Snow JB (2003) Ballenger's otorhinolaryngology: head and neck surgery. Pmph-usa
Bared A, Ouyang X, Angeli S, Du LL, Hoang K, Yan D, Liu XZ (2010) Antioxidant enzymes, presbycusis, and ethnic variability. Otolaryngol Head Neck Surg 143:263–268
Beresford AP (1993) CYP1A1: friend or foe? Drug Metab Rev 25:503–517
Bovo R, Ciorba A, Martini A (2011) Environmental and genetic factors in age-related hearing impairment. Aging Clin Exp Res 23:3–10
Bromberg Y, Rost B (2007) SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res 35:3823–3835
Chatr-Aryamontri A, Breitkreutz B-J, Oughtred R, Boucher L, Heinicke S, Chen D, Stark C, Breitkreutz A, Kolas N, O'Donnell L (2015) The BioGRID interaction database: 2015 update. Nucleic Acids Res 43:D470–D478
Christensen K, Frederiksen H, Hoffman HJ (2001) Genetic and environmental influences on self-reported reduced hearing in the old and oldest old. J Am Geriatr Soc 49:1512–1517
Coling DE, Kenneth C, Somand D, Satar B, Bai U, Huang T-T, Seidman MD, Epstein CJ, Mhatre AN, Lalwani AK (2003) Effect of SOD1 overexpression on age-and noise-related hearing loss. Free Radic Biol Med 34:873–880
Cruickshanks KJ, Wiley TL, Tweed TS, Klein BE, Klein R, Mares-Perlman JA, Nondahl DM (1998) Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin: The epidemiology of hearing loss study. Am J Epidemiol 148:879–886
Duell EJ, Holly EA, Bracci PM, Liu M, Wiencke JK, Kelsey KT (2002) A population-based, case–control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. J Natl Cancer Inst 94:297–306
El Barbary A, Altschuler RA, Schacht J (1993) Glutathione S-transferases in the organ of Corti of the rat: enzymatic activity, subunit composition and immunohistochemical localization. Hear Res 71:80–90
Gates GA, Couropmitree NN, Myers RH (1999) Genetic associations in age-related hearing thresholds. Archives of otolaryngology–head & neck surgery 125:654–659
Gonzalez FJ (1990) Molecular genetics of the P-450 superfamily. Pharmacol Ther 45:1–38
Hayashi S-I, Watanabe J, Nakachi K, Kawajiri K (1991) PCR detection of an A/G polymorphism within exon 7 of the CYP1A1 gene. Nucleic Acids Res 19:4797
Huang Q, Tang J (2010) Age-related hearing loss or presbycusis. Eur Arch Otorhinolaryngol 267:1179–1191
Karimian M, Momeni A, Farmohammadi A, Behjati M, Jafari M, Raygan F (2020) Common gene polymorphism in ATP-binding cassette transporter A1 and coronary artery disease: a genetic association study and a structural analysis. J Cell Biochem 121:3345–3357
Landi M, Bertazzi P, Shields PG, Clark G, Lucier G, Garte S, Cosma G, Caporaso N (1994) Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans. Pharmacogenetics 4:242–246
Lautermann J, McLaren J, Schacht J (1995) Glutathione protection against gentamicin ototoxicity depends on nutritional status. Hear Res 86:15–24
Liberman MC, Kujawa SG (2017) Cochlear synaptopathy in acquired sensorineural hearing loss: manifestations and mechanisms. Hear Res 349:138–147
Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795
Lin FR, Maas P, Chien W, Carey JP, Ferrucci L, Thorpe R (2012) Association of skin color, race/ethnicity, and hearing loss among adults in the USA. J Assoc Res Otolaryngol 13:109–117
Liu XZ, Yan D (2007) Ageing and hearing loss. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland 211:188–197
Liu H, Shi L, Giesy JP, Yu H (2019) Polychlorinated diphenyl sulfides can induce ROS and genotoxicity via the AhR-CYP1A1 pathway. Chemosphere 223:165–170
Manche SK, Jangala M, Putta P, Koralla RM, Akka J (2016) Association of oxidative stress gene polymorphisms with presbycusis. Gene 593:277–283
Mobasseri N, Nikzad H, Karimian M (2019) Protective effect of oestrogen receptor α-PvuII transition against idiopathic male infertility: a case-control study and meta-analysis. Reprod BioMed Online 38:588–598
Noureddini M, Mobasseri N, Karimian M, Behjati M, Nikzad H (2018) Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis. The Journal of Gene Medicine 20:e3053
Ohlemiller KK (2009) Mechanisms and genes in human strial presbycusis from animal models. Brain Res 1277:70–83
Organization WH (2017): Deafness and hearing loss. Fact sheet. Geneva, Switzerland: Author
Parl FF (2005) Glutathione S-transferase genotypes and cancer risk. Cancer Lett 221:123–129
Rabinowitz PM, Wise JP Sr, Mobo BH, Antonucci PG, Powell C, Slade M (2002) Antioxidant status and hearing function in noise-exposed workers. Hear Res 173:164–171
Riva C, Donadieu E, Magnan J, Lavieille J-P (2007) Age-related hearing loss in CD/1 mice is associated to ROS formation and HIF target proteins up-regulation in the cochlea. Exp Gerontol 42:327–336
Sabarinathan R, Tafer H, Seemann SE, Hofacker IL, Stadler PF, Gorodkin J (2013) The RNAsnp web server: predicting SNP effects on local RNA secondary structure. Nucleic Acids Res 41:W475–W479
Salimi S, Keshavarzi F, Mohammadpour-Gharehbagh A, Moodi M, Mousavi M, Karimian M, Sandoughi M (2017) Polymorphisms of the folate metabolizing enzymes: association with SLE susceptibility and in silico analysis. Gene 637:161–172
Shimokata H (2008) Why are individual differences in the hearing ability so great in the elderly? Audiology Japan 51:177–184
Staecker QYZ, Van De Water Thomas R, Hinrich (2001) Oxidative stress in aging in the C57B16/J mouse cochlea. Acta Otolaryngol 121:666–672
Tameh AA, Karimian M, Zare-Dehghanani Z, Aftabi Y, Beyer C (2018) Role of steroid therapy after ischemic stroke by n-methyl-d-aspartate receptor gene regulation. J Stroke Cerebrovasc Dis 27:3066–3075
Tavanai E, Mohammadkhani G (2017) Role of antioxidants in prevention of age-related hearing loss: a review of literature. Eur Arch Otorhinolaryngol 274:1821–1834
Uno S, Dalton TP, Derkenne S, Curran CP, Miller ML, Shertzer HG, Nebert DW (2004) Oral exposure to benzo [a] pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation. Mol Pharmacol 65:1225–1237
Van Eyken E, Van Camp G, Fransen E, Topsakal V, Hendrickx JJ, Demeester K, Van de Heyning P, Mäki-Torkko E, Hannula S, Sorri M (2007) Contribution of the N-acetyltransferase 2 polymorphism NAT2* 6A to age-related hearing impairment. J Med Genet 44:570–578
Yamasoba T, Nuttall AL, Harris C, Raphael Y, Miller JM (1998) Role of glutathione in protection against noise-induced hearing loss. Brain Res 784:82–90
Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K (2013) Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. Hear Res 303:30–38
Zamani-Badi T, Nikzad H, Karimian M (2018) IL-1RA VNTR and IL-1α 4845G> T polymorphisms and risk of idiopathic male infertility in Iranian men: a case–control study and an in silico analysis. Andrologia 50:e13081
Acknowledgments
The authors thank all participants in this study.
Funding
This study was supported by Grants from the Kashan University of Medical Sciences (Grant no. 97116).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Responsible editor: Lotfi Aleya
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Karimian, M., Behjati, M., Barati, E. et al. CYP1A1 and GSTs common gene variations and presbycusis risk: a genetic association analysis and a bioinformatics approach. Environ Sci Pollut Res 27, 42600–42610 (2020). https://doi.org/10.1007/s11356-020-10144-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-020-10144-0