CYP1A1 and GSTs common gene variations and presbycusis risk: a genetic association analysis and a bioinformatics approach

• Published in: Environmental science and pollution research international Vol. 27; no. 34; pp. 42600 - 42610
• Main Authors: Karimian, Mohammad, Behjati, Mohaddeseh, Barati, Erfaneh, Ehteram, Tayyebeh, Karimian, Ali
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2020; Springer Nature B.V
• Subjects: Antioxidants; Aquatic Pollution; Association analysis; Atmospheric Protection/Air Quality Control/Air Pollution; Bioinformatics; Case-Control Studies; Computational Biology; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P450; Cytochromes P450; Cytotoxicity; Deletion; Detoxification; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Environmental science; Enzymes; Genetic analysis; Genetic Predisposition to Disease; Genotype; Genotypes; Glutathione; Glutathione transferase; Glutathione Transferase - genetics; GSTM1 protein; GSTT1 protein; Humans; Iran; Metabolism; Nucleotides; Oxidative stress; Polymerase chain reaction; Presbycusis - genetics; Reactive oxygen species; Research Article; Restriction fragment length polymorphism; Ribonucleic acid; Risk analysis; Risk Factors; RNA; Single-nucleotide polymorphism; Waste Water Technology; Water Management; Water Pollution Control; Iran; Oxidative stress; Genetic association; gene; genes; Presbycusis; Genetic polymorphism; CYP1A1 gene; GST genes
• ISSN: 0944-1344; 1614-7499
• DOI: 10.1007/s11356-020-10144-0

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 GST s ( 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.