Polymorphisms and allele frequencies of glutathione S-transferases A1 and P1 genes in the Polish population

Skrzypczak-Zielińska, Marzena; Zakerska-Banaszak, Oliwia; Tamowicz, Barbara; Sobieraj, I; Drwęska-Matelska, Natalia; Szalata, Marlena; Słomski, Ryszard; Mikstacki, Adam

doi:10.4238/2015.march.31.15

Cited by 5 publications

(7 citation statements)

References 35 publications

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“…The frequency of the GSTA1*B*B observed in our validation healthy subject cohort (20%) was almost identical to the one observed in two other Caucasian populations (20 and 20.8%, respectively) [41,42]. In our adult study cohort receiving busulfan, the *B variant was found in slightly higher frequency (26% for the *B*B genotype).…”

Section: Discussionsupporting

confidence: 85%

Impact of GSTA1 Polymorphisms on Busulfan Oral Clearance in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation

et al. 2019

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Background: Busulfan pharmacokinetics exhibit large inter-subject variability. Our objective was to evaluate the influence of glutathione S-transferase A1 (GSTA1) gene variants on busulfan oral clearance (CLo) in a population of patients undergoing hematopoietic stem cell transplantation. Methods: This is a quasi-experimental retrospective study in adult patients (n = 87 included in the final analyses) receiving oral busulfan. Pharmacokinetics data (area under the plasma concentration-time curve (AUC) determined from 10 blood samples) were retrieved from patients’ files and GSTA1 *A and *B allele polymorphisms determined from banked DNA samples. Three different limited sampling methods (LSM) using four blood samples were also compared. Results: Carriers of GSTA1*B exhibited lower busulfan CLo than patients with an *A/*A genotype (p < 0.002): Busulfan CLo was 166 ± 31, 187 ± 37 vs. 207 ± 47 mL/min for GSTA1*B/*B, *A/*B and *A/*A genotypes, respectively. Similar results were obtained with the tested LSMs. Using the standard AUC method, distribution of patients above the therapeutic range after the first dose was 29% for GSTA1*A/*A, 50% for *A/*B, and 65% for *B/*B. The LSMs correctly identified ≥91% of patients with an AUC above the therapeutic range. The misclassified patients had a mean difference less than 5% in their AUCs. Conclusion: Patients carrying GSTA1 loss of function *B allele were at increased risk of overdosing on their initial busulfan oral dose. Genetic polymorphisms associated with GSTA1 explain a significant part of busulfan CLo variability which could be captured by LSM strategies.

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Section: Discussionsupporting

confidence: 85%

Impact of GSTA1 Polymorphisms on Busulfan Oral Clearance in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation

et al. 2019

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“…Genomic DNA for molecular analysis was obtained from peripheral blood samples according to standard procedures using the method with guanidine isothiocyanate (GTC). Analysis of GSTA1 promoter variants (in positions −52, −69 and −567) and two substitutions (c.313A>G and c.341C>T) in GSTP1 gene was performed using sequencing and pyrosequencing respectively, as was described previously [ 20 ]. For genotyping of promoter SNP -1053C>T in the CYP2E1 gene we used the pyrosequencing technique.…”

Section: Methodsmentioning

confidence: 99%

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

Mikstacki¹,

Skrzypczak-Zielińska

Zakerska-Banaszak

et al. 2016

BMC Med Genet

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BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionsGSTP1 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.

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“…Genetic variations in the genes encoding enzymes that metabolize xenobiotics may alter the expression level of the protein product, thereby affecting an individual's susceptibility to various diseases and carcinogens and influencing the efficacy and toxicity of certain drugs [1]. As mentioned above, the frequencies of GSTA1 C-69T polymorphism can be variable among distinct populations, which may lead to intra-and interpopulation distinctions in xenobiotic-induced toxic effects.…”

Section: P a G E | 224mentioning

confidence: 99%

“…One of the main groups of phase II enzymes is glutathione Stransferases (GSTs). GSTs play a significant role in the detoxification and metabolism of endogenous and exogenous substances that include a wide range of medications, products of oxidative stress, carcinogens, environmental toxins by catalyzing the conjugation between electrophilic substances and reduced glutathione [1,2]. Different GST isoenzymes have been identified in humans.…”

Section: Introductionmentioning

confidence: 99%

Frequencies of glutathione S-transferase A1 rs3957357 polymorphism in a Turkish population

Şahinoğulları¹

2021

Journal of Surgery and Medicine

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Background/Aim: Glutathione-S-transferases (GSTs), a major group of phase II enzymes, play a significant role in the detoxification and metabolism of endogenous and exogenous compounds. The objective of the survey was to identify the distribution of genotype and allele frequencies of GSTA1 -69C>T (rs3957357) polymorphism in a healthy Turkish population and compare the determined frequencies with those in various populations. Methods: Polymerase chain reaction and restriction fragment length polymorphism methods were used to analyze GSTA1 -69C>T polymorphism in DNA samples of 105 healthy Turkish individuals. Results: The distribution of GSTA1 CC, CT, and TT genotype frequencies were 32.4%, 48.6% and 19.0%, respectively while the allele frequencies were 56.7% for C allele and 43.3% for T allele. The findings obtained were compared with the results of various populations. The frequencies of GSTA1 -69C>T polymorphism were similar to those of the African American population and the populations with White ancestry, but significantly different from those reported for the populations with Asian ancestry. Conclusion:To the best of our knowledge, this is the first study to present the frequencies of the GSTA1 -69C>T polymorphism among Turkish individuals. The findings of the current study may provide a perspective for further studies exploring the role of GSTA1 -69C>T polymorphism on predisposition to diverse illnesses such as cancer and may be used as a control group for such studies. In addition, this study might contribute to epidemiological and toxicogenetic investigations.

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Polymorphisms and allele frequencies of glutathione S-transferases A1 and P1 genes in the Polish population

Cited by 5 publications

References 35 publications

Impact of GSTA1 Polymorphisms on Busulfan Oral Clearance in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation

Impact of GSTA1 Polymorphisms on Busulfan Oral Clearance in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation

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

Frequencies of glutathione S-transferase A1 rs3957357 polymorphism in a Turkish population

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