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EPHX1、GSTP1、GSTM1和GSTT1基因多态性与慢性阻塞性肺疾病抗氧化应激标志物的相关性

Correlation of EPHX1, GSTP1, GSTM1, and GSTT1 genetic polymorphisms with antioxidative stress markers in chronic obstructive pulmonary disease.

作者信息

Lakhdar Ramzi, Denden Sabri, Mouhamed Manel Haj, Chalgoum Abdelkader, Leban Nadia, Knani Jalel, Lefranc Gérard, Miled Abelhadi, Ben Chibani Jemni, Khelil Amel Haj

机构信息

Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, Monastir, Tunisia.

出版信息

Exp Lung Res. 2011 May;37(4):195-204. doi: 10.3109/01902148.2010.535093. Epub 2011 Feb 11.

Abstract

This study was undertaken to ascertain if a relationship existed between oxidative status and polymorphisms of microsomal epoxide hydrolase X1 (EPHX1), glutathione S-transferase P1 (GSTP1), GSTM1, and GSTT1 in chronic obstructive pulmonary disease (COPD). Erythrocyte glutathione peroxidase (GSH-px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and plasma GST activities and total antioxidant status (TAS) as antioxidative stress markers were determined and compared either with individual and combined genotypes of EPHX1 exon 3, GSTP1 exon 5, GSTM1, and GSTT1 polymorphisms in COPD patients and healthy controls from the central area of Tunisia. Statistical data processing revealed significantly lower GSH-px, GR, SOD, CAT, GST, and TAS values in COPD patients in comparison to the control group (P < .001). As for genotypes, there was a no significant association in each of the 6 parameters and individual genotypes (P > .05). A significant correlation between the studied parameters and combined null GSTM1/null GSTT1 (GSH-px: P < .001, GR: P = .026, CAT: P = .018, GST: P = .022, TAS: P = .046), His113His EPHX1/null GSTM1 (GSH-px: P = .001, GST: P = .0012, TAS: P = .013), His113His EPHX1/Val105Val GSTP1 (GSH-px: P = .048, CAT: P = .026, GST: P = .031), and null GSTM1/Val105Val GSTP1 (GSH-px: P = .011, GR: P = .0028, GST: P = .0054, TAS: P = .032) was found in patients. In conclusion, combined genetic polymorphisms of GSTM1, GSTT1, GSTP1, and EPHX1 may have favorable effects on redox balance in COPD patients.

摘要

本研究旨在确定慢性阻塞性肺疾病(COPD)患者的氧化状态与微粒体环氧化物水解酶X1(EPHX1)、谷胱甘肽S-转移酶P1(GSTP1)、GSTM1和GSTT1基因多态性之间是否存在关联。测定了红细胞谷胱甘肽过氧化物酶(GSH-px)、谷胱甘肽还原酶(GR)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)以及血浆GST活性和总抗氧化状态(TAS)作为抗氧化应激标志物,并将其与突尼斯中部地区COPD患者和健康对照者的EPHX1第3外显子、GSTP1第5外显子、GSTM1和GSTT1基因多态性的个体及组合基因型进行比较。统计数据处理显示,与对照组相比,COPD患者的GSH-px、GR、SOD、CAT、GST和TAS值显著降低(P < .001)。至于基因型,在6个参数中的每一个参数与个体基因型之间均无显著关联(P > .05)。在患者中发现,所研究的参数与GSTM1基因缺失/GSTT1基因缺失组合(GSH-px:P < .001,GR:P = .026,CAT:P = .018,GST:P = .022,TAS:P = .046)、His113His EPHX1/GSTM1基因缺失组合(GSH-px:P = .001,GST:P = .0012,TAS:P = .013)、His113His EPHX1/Val105Val GSTP1组合(GSH-px:P = .048,CAT:P = .026,GST:P = .031)以及GSTM1基因缺失/Val105Val GSTP1组合(GSH-px:P = .011,GR:P = .0028,GST:P = .0054,TAS:P = .032)之间存在显著相关性。总之,GSTM1、GSTT1、GSTP1和EPHX1的联合基因多态性可能对COPD患者的氧化还原平衡产生有利影响。

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