title: Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Regional Hospital, Juraszow 7/19, 60-479, Poznan, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Mikstacki
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Skrzypczak-Zielinska
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.|The NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614, Poznan, Poland.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Zakerska-Banaszak
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Regional Hospital, Juraszow 7/19, 60-479, Poznan, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tamowicz
authors.affiliation: Department of Genetics in Psychiatry, University of Medical Sciences, Szpitalna 27/33, 60-572, Poznan, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Skibinska
authors.affiliation: Department of Computer Science and Statistics, University of Medical Sciences, Dabrowskiego 79, 60-529, Poznan, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Molinska-Glura
authors.affiliation: Department of Biochemistry and Biotechnology, University of Life Sciences, Dojazd 11, 60-632, Poznan, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Szalata
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland. slomski@up.poznan.pl.|Department of Biochemistry and Biotechnology, University of Life Sciences, Dojazd 11, 60-632, Poznan, Poland. slomski@up.poznan.pl.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Slomski
mesh_terms: D000328:Adult; D000368:Aged; D000768:Anesthesia, General / Q000379:methods; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000097:blood* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D000077149:Sevoflurane; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D008738:Methyl Ethers; D000077149:Sevoflurane; D019392:Cytochrome P-450 CYP2E1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha
keywords: CYP2E1; GSTA1; GSTP1; Hepatotoxicity; Polymorphism; Sevoflurane; α-GST