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Published in: BMC Medical Genetics 1/2016

Open Access 01-12-2016 | Research article

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia

Authors: Adam Mikstacki, Marzena Skrzypczak-Zielinska, Oliwia Zakerska-Banaszak, Barbara Tamowicz, Maria Skibinska, Marta Molinska-Glura, Marlena Szalata, Ryszard Slomski

Published in: BMC Medical Genetics | Issue 1/2016

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Abstract

Background

The serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane.

Methods

The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated.

Results

The allele GSTA1*B (−567G, −69T, −52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia.

Conclusions

GSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.
Literature
1.
go back to reference Yousif MA, Khafagy HF, El-Shanawani FM, El-Sabae HH, Omar SH, Allam MN, et al. Hepatocellular integrity during sevoflurane anesthesia with induced hypotension. J Egypt Soc Parasitol. 2009;39:641–51.PubMed Yousif MA, Khafagy HF, El-Shanawani FM, El-Sabae HH, Omar SH, Allam MN, et al. Hepatocellular integrity during sevoflurane anesthesia with induced hypotension. J Egypt Soc Parasitol. 2009;39:641–51.PubMed
2.
go back to reference Suttner SW, Schmidt CC, Boldt J, Hüttner I, Kumle B, Piper SN. Low-flow desflurane and sevoflurane anesthesia minimally affect hepatic integrity and function in elderly patients. Anesth Analg. 2000;91:206–12.PubMed Suttner SW, Schmidt CC, Boldt J, Hüttner I, Kumle B, Piper SN. Low-flow desflurane and sevoflurane anesthesia minimally affect hepatic integrity and function in elderly patients. Anesth Analg. 2000;91:206–12.PubMed
3.
go back to reference Ray DC, Bomont R, Mizushima A, Kugimiya T, Howie AF, Beckett GJ. Effect of sevoflurane anaesthesia on plasma concentrations of glutathione S-transferase. Br J Anaesth. 1996;77:404–7.CrossRefPubMed Ray DC, Bomont R, Mizushima A, Kugimiya T, Howie AF, Beckett GJ. Effect of sevoflurane anaesthesia on plasma concentrations of glutathione S-transferase. Br J Anaesth. 1996;77:404–7.CrossRefPubMed
4.
go back to reference Goldberg ME, Cantillo J, Gratz I, Deal E, Vekeman D, McDougall R, et al. Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers. Anesth Analg. 1999;88:437–45.PubMed Goldberg ME, Cantillo J, Gratz I, Deal E, Vekeman D, McDougall R, et al. Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers. Anesth Analg. 1999;88:437–45.PubMed
5.
go back to reference Tiainen P, Lindgren L, Rosenberg PH. Changes in hepatocellular integrity during and after desflurane or isoflurane anaesthesia in patients undergoing breast surgery. Br J Anaesth. 1998;80:87–9.CrossRefPubMed Tiainen P, Lindgren L, Rosenberg PH. Changes in hepatocellular integrity during and after desflurane or isoflurane anaesthesia in patients undergoing breast surgery. Br J Anaesth. 1998;80:87–9.CrossRefPubMed
6.
go back to reference Arslan M, Kurtipek O, Dogan AT, Unal Y, Kizil Y, Nurlu N, et al. Comparison of effects of anaesthesia with desflurane and enflurane on liver function. Singapore Med J. 2009;50:73.PubMed Arslan M, Kurtipek O, Dogan AT, Unal Y, Kizil Y, Nurlu N, et al. Comparison of effects of anaesthesia with desflurane and enflurane on liver function. Singapore Med J. 2009;50:73.PubMed
7.
go back to reference Taivainen T, Tiainen P, Meretoja OA, Räihä L, Rosenberg PH. Comparison of the effects of sevoflurane and halothane on the quality of anaesthesia and serum glutathione transferase alpha and fluoride in paediatric patients. Br J Anaesth. 1994;73:590–5.CrossRefPubMed Taivainen T, Tiainen P, Meretoja OA, Räihä L, Rosenberg PH. Comparison of the effects of sevoflurane and halothane on the quality of anaesthesia and serum glutathione transferase alpha and fluoride in paediatric patients. Br J Anaesth. 1994;73:590–5.CrossRefPubMed
8.
go back to reference Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30:445–600.CrossRefPubMed Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30:445–600.CrossRefPubMed
9.
go back to reference Koo DJ, Zhou M, Chaudry IH, Wang P. Plasma alpha-glutathione S-transferase: a sensitive indicator of hepatocellular damage during polymicrobial sepsis. Arch Surg. 2000;135:198–203.CrossRefPubMed Koo DJ, Zhou M, Chaudry IH, Wang P. Plasma alpha-glutathione S-transferase: a sensitive indicator of hepatocellular damage during polymicrobial sepsis. Arch Surg. 2000;135:198–203.CrossRefPubMed
10.
go back to reference Morel F, Rauch C, Coles B, Le Ferrec E, Guillouzo A. The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. Pharmacogenetics. 2002;12:277–86.CrossRefPubMed Morel F, Rauch C, Coles B, Le Ferrec E, Guillouzo A. The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. Pharmacogenetics. 2002;12:277–86.CrossRefPubMed
11.
go back to reference Moscow JA, Fairchild CR, Madden MJ, Ransom DT, Wieand HS, O’Brien EE, et al. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 1989;49:1422–8.PubMed Moscow JA, Fairchild CR, Madden MJ, Ransom DT, Wieand HS, O’Brien EE, et al. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 1989;49:1422–8.PubMed
12.
go back to reference Eger 2nd EI, Koblin DD, Bowland T, Ionescu P, Laster MJ, Fang Z, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg. 1997;84:160–8.PubMed Eger 2nd EI, Koblin DD, Bowland T, Ionescu P, Laster MJ, Fang Z, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg. 1997;84:160–8.PubMed
13.
go back to reference Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19:275–80.CrossRefPubMed Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19:275–80.CrossRefPubMed
14.
go back to reference Canto P, Canto-Cetina T, Juárez-Velázquez R, Rosas-Vargas H, Rangel-Villalobos H, Canizales-Quinteros S, et al. Methylenetetrahydrofolate reductase C677T and glutathione S-transferase P1 A313G are associated with a reduced risk of preeclampsia in Maya-Mestizo women. Hypertens Res. 2008;31:1015–9.CrossRefPubMed Canto P, Canto-Cetina T, Juárez-Velázquez R, Rosas-Vargas H, Rangel-Villalobos H, Canizales-Quinteros S, et al. Methylenetetrahydrofolate reductase C677T and glutathione S-transferase P1 A313G are associated with a reduced risk of preeclampsia in Maya-Mestizo women. Hypertens Res. 2008;31:1015–9.CrossRefPubMed
15.
go back to reference Board PG, Webb GC, Coggan M. Isolation of a cDNA clone and localization of the human glutathione S-transferase 3 genes to chromosome bands 11q13 and 12q13-14. Ann Hum Genet. 1989;53:205–13.CrossRefPubMed Board PG, Webb GC, Coggan M. Isolation of a cDNA clone and localization of the human glutathione S-transferase 3 genes to chromosome bands 11q13 and 12q13-14. Ann Hum Genet. 1989;53:205–13.CrossRefPubMed
16.
go back to reference Harries LW, Stubbins MJ, Forman D, Howard GC, Wolf CR. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis. 1997;18:641–4.CrossRefPubMed Harries LW, Stubbins MJ, Forman D, Howard GC, Wolf CR. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis. 1997;18:641–4.CrossRefPubMed
17.
go back to reference Ingelman-Sundberg M. Polymorphism of cytochrome P450 and xenobiotic toxicity. Toxicology. 2002;181–182:447–52.CrossRefPubMed Ingelman-Sundberg M. Polymorphism of cytochrome P450 and xenobiotic toxicity. Toxicology. 2002;181–182:447–52.CrossRefPubMed
18.
go back to reference Restrepo JG, Garcia-Martin E, Martinez C, Agundez JAG. Polymorphic drug metabolism in anaesthesia. Curr Drug Met. 2009;10:236–46.CrossRef Restrepo JG, Garcia-Martin E, Martinez C, Agundez JAG. Polymorphic drug metabolism in anaesthesia. Curr Drug Met. 2009;10:236–46.CrossRef
19.
go back to reference Mikstacki A, Skrzypczak-Zielinska M, Tamowicz B, Zakerska-Banaszak O, Szalata M, Slomski R. The impact of genetic factors on response to anaesthetics. Adv Med Sci. 2013;58:9–14.CrossRefPubMed Mikstacki A, Skrzypczak-Zielinska M, Tamowicz B, Zakerska-Banaszak O, Szalata M, Slomski R. The impact of genetic factors on response to anaesthetics. Adv Med Sci. 2013;58:9–14.CrossRefPubMed
20.
go back to reference Skrzypczak-Zielinska M, Zakerska-Banaszak O, Tamowicz B, Sobieraj I, Drweska-Matelska N, Szalata M, et al. Polymorphisms and allele frequencies of Glutathione S-transferases A1 and P1 genes in the Polish population. Genomics Mol Res. 2015;14:2850–9.CrossRef Skrzypczak-Zielinska M, Zakerska-Banaszak O, Tamowicz B, Sobieraj I, Drweska-Matelska N, Szalata M, et al. Polymorphisms and allele frequencies of Glutathione S-transferases A1 and P1 genes in the Polish population. Genomics Mol Res. 2015;14:2850–9.CrossRef
21.
go back to reference Rosner B. Fundamentals of Biostatistics. Brooks/Cole Cengage Learning: Boston, USA; 2010. Rosner B. Fundamentals of Biostatistics. Brooks/Cole Cengage Learning: Boston, USA; 2010.
22.
go back to reference Mikstacki A, Zakerska-Banaszak O, Skrzypczak-Zielinska M, Tamowicz B, Szalata M, Slomski R. Glutathione S-transferase as a toxicity indicator in general anesthesia: genetics and biochemical function. J Clin Anesth. 2015;27:73–9.CrossRefPubMed Mikstacki A, Zakerska-Banaszak O, Skrzypczak-Zielinska M, Tamowicz B, Szalata M, Slomski R. Glutathione S-transferase as a toxicity indicator in general anesthesia: genetics and biochemical function. J Clin Anesth. 2015;27:73–9.CrossRefPubMed
23.
go back to reference Kaymak C, Karahalil B, Ozcan NN, Oztuna D. Association between GSTP1 gene polymorphism and serum alpha-GST concentrations undergoing sevoflurane anaesthesia. Eur J Anaesthesiol. 2008;25:193–9.CrossRefPubMed Kaymak C, Karahalil B, Ozcan NN, Oztuna D. Association between GSTP1 gene polymorphism and serum alpha-GST concentrations undergoing sevoflurane anaesthesia. Eur J Anaesthesiol. 2008;25:193–9.CrossRefPubMed
24.
go back to reference Hongo T. Sevoflurane reduced but isoflurane maintained hepatic blood flow during anesthesia in man. J Anesth. 1994;8:55–9.CrossRef Hongo T. Sevoflurane reduced but isoflurane maintained hepatic blood flow during anesthesia in man. J Anesth. 1994;8:55–9.CrossRef
Metadata
Title
Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia
Authors
Adam Mikstacki
Marzena Skrzypczak-Zielinska
Oliwia Zakerska-Banaszak
Barbara Tamowicz
Maria Skibinska
Marta Molinska-Glura
Marlena Szalata
Ryszard Slomski
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2016
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-016-0302-6

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