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The Cu/Zn superoxide dismutase +35A/C (rs2234694) variant correlates with altered levels of protein carbonyls and glutathione and associates with severity of COPD in a Tunisian population
Authors:Amel Ben Anes  Hela Ben Nasr  Abdelhamid Garrouche  Sarra Bchir  Zaineb Dhaouefi  Elyes Chabchoub
Institution:1. Unité de recherche UR12ES06 Physiologie de l’Exercice et Physiopathologie: de l’Intégré au Moléculaire ? Biologie, Médecine et Santé ?, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia;2. Service de Pneumo-Allergologie Centre hospitalier universitaire Farhat Hached, Sousse, Tunisia;3. Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Monastir, Tunisia;4. Unité de Recherche 04/UR/08-05 Molecular Immunogenetics Faculté de Médecine, Sousse, Tunisia
Abstract:Chronic obstructive pulmonary disease (COPD) is a major cause of mortality that has been associated with inflammation and oxidative stress. The purpose of the present case–control study was to determine the relationships between oxidative stress-related genetic variants and the risk and severity of COPD, as well as, the influence of these variants on inflammatory and oxidative stress parameters. Genotyping of superoxide dismutase 1 (SOD1) + 35 A/C (rs2234694), catalase A-21T (rs7943316), C-262T (rs1001179)] and glutathione peroxidase 1 (reduced glutathione (GSH)-Px1) 198Pro/Leu (rs1050450) was carried out in 143 patients with COPD and 216 healthy controls using PCR-RFLP. Serum levels of IL-6 and TNF-α were determined by enzyme-linked immunosorbent assays (ELISA), while the levels of reduced GSH, total antioxidant status (TAS), H2O2, lipid peroxides (TBARS) and protein carbonyls (PCs) were determined using spectrophotometric methods. We also evaluated the activities of GSH-Px, catalase, and superoxide dismutase (SOD) in both plasma and erythrocytes. We did not observe significant differences in the genotype and allele frequencies of chosen variants between COPD patients and healthy controls. A significant correlation was retrieved between the SOD1?+?35A/C variant and disease severity (odds ratios (OR) = 0.15, p?=?0.04). In addition, patients having the +35AC genotype presented increased plasma levels of GSH and a reduced level of PCs (p?=?0.03, p?=?0.04, respectively). The present data highlighted the important role of antioxidant enzymes and their genetic variants in the oxidative stress-mediated pathogenesis and progression of COPD.
Keywords:Catalase  COPD  genetic variants  GSH-Px  oxidative stress  SOD
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