Mikstacki Adam, Skrzypczak-Zielinska Marzena, Zakerska-Banaszak Oliwia, Tamowicz Barbara, Skibinska Maria, Molinska-Glura Marta, Szalata Marlena, Slomski Ryszard
Department of Anaesthesiology and Intensive Therapy, Regional Hospital, Juraszow 7/19, 60-479, Poznan, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
BMC Med Genet. 2016 May 14;17(1):40. doi: 10.1186/s12881-016-0302-6.
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.
血清谷胱甘肽S-转移酶α（α-GST）浓度已被用作肝脏状况的标志物。七氟醚麻醉后，观察到肝细胞完整性有轻度损害。CYP2E1、GSTA1和GSTP1基因的遗传多态性会影响酶的活性，可能会影响七氟醚的肝毒性作用。本研究的目的是评估CYP2E1、GSTA1和GSTP1基因的遗传多态性对86例ASA身体状况为I-II级、在全身麻醉下使用七氟醚进行喉科手术的非亲属患者血清α-GST水平的影响。
使用酶联免疫吸附测定法（ELISA）分析三个围手术期时间点的血清样本。通过焦磷酸测序和测序检测基因变异。最后，估计血清α-GST浓度与CYP2E1、GSTP1和GSTA1基因分析等位基因之间的统计关联。
GSTA1*B（-567G、-69T、-52A）等位基因频率为0.43，而GSTP1的c.313G和c.341T等位基因频率分别为0.28和0.1。观察到CYP2E1基因的-1053T等位基因频率为0.01。我们发现，与麻醉前和麻醉后24小时时间点的水平相比，GSTP1基因纯合变化c.313A>G和c.341C>T时，麻醉结束时血清α-GST浓度显著更高。此外，GSTA1野生型基因型与麻醉结束后24小时α-GST浓度升高有关。
GSTP1基因多态性对接受七氟醚麻醉的患者围手术期血清α-GST浓度有影响。GSTA1基因变异与围手术期血清α-GST水平之间存在类似关联，尽管无统计学意义。
