Experimental Lung Research, 37, 195–204, 2011 Copyright © Informa Healthcare USA, Inc. ISSN: 0190-2148 print / 1521-0499 online DOI: 10.3109/01902148.2010.535093 Correlation of EPHX1, GSTP1, GSTM1, and GSTT1 genetic polymorphisms with antioxidative stress markers in chronic obstructive pulmonary disease Ramzi Lakhdar, 1 Sabri Denden, 1 Manel Haj Mouhamed, 2 Abdelkader Chalgoum, 2 Nadia Leban, 1 Jalel Knani, 3 G´ erard Lefranc, 4 Abelhadi Miled, 2 Jemni Ben Chibani, 1 and Amel Haj Khelil 1 1 Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, Monastir, Tunisia 2 Biochemistry Laboratory, CHU Farhat Hached, Sousse, Tunisia 3 Department of Pulmonology, CHU Tahar Sfar, Mahdia, Tunisia 4 Institute of Human Genetics and Montpellier 2 University, Montpellier, France 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 re- ductase (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 com- bined 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 signifcantly 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 signifcant association in each of the 6 parameters and individual genotypes (P > .05). A signifcant 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. KEYWORDS COPD, genetic polymorphism, glutathione S-transferase, microsomal epoxide hydrolase, oxidative stress Chronic obstructive pulmonary disease (COPD) is a slowly progressive and poorly reversible infam- matory disease. It is characterized by a functional abnormality of airway obstruction, which includes emphysema, chronic bronchitis, and small airways disease [1]. Tobacco smoking is the most important risk factor for the development of COPD. However, only 10% to 15% of smokers develop the disease, which imply contribution of genetic factors [2]. Received 3 July 2010; accepted 12 October 2010 Address correspondence to Ramzi Lakhdar, Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, 1, Av. Avicenne, 5019 Monastir, Tunisia. E-mail: lakhdarramzi@yahoo.fr Despite that the pathogenesis of COPD remains incompletely understood, three processes contribut- ing to the disease are well established [3]. As a frst mechanism, there is an infux of infammatory cells into the airways and lungs caused by the inhalation of noxious particles such as cigarette smoke leading to chronic infammation [3]. The second described process was a disruption of the balance between pro- teolytic and antiproteolytic molecules in the lungs of COPD patients that occurs as a result of an increased proteolytic activity [4]. This causes the destruction of healthy lung parenchyma, which leads to the develop- ment of emphysema. The third mechanism involved in this pathogenesis is oxidative stress, which occurs 195