One of pathogenesis of COPD is

One of pathogenesis of COPD is oxidant/antioxidant imbalance. Indeed, it is well known that chronic tobacco smoking is a major risk factor for the development of COPD, and a defect in the detoxification of reactive species produced by cigarette smoke may predispose smokers to airflow obstruction and emphysema [2]. Potential explanations for why some cigarette smokers acquire chronic airways disease but not others include genetic differences in inflammatory and repair processes and/or modulation of these responses by infections or other environmental insults suggesting that individual susceptibility or genetic factors may play a role [3]. Several candidate genes such as α-1-antitrypsin (AAT), tumor necrosis factor α (TNF-α), heme oxygenase-1 (HMOX), cytochrome P450, and microsomal epoxide hydrolase (mEPHX) that could be involved in the development of COPD were investigated. Among the genes that contribute to xenobiotic metabolism and susceptibility to COPD, the glutathione S-transferase (GST) gene family is one of the most studied in diverse human populations [2]. GST is a family of enzymes comprising 16 genes in six subfamilies [alpha (GSTA), mu (GSTM), omega (GSTO), pi (GSTP), theta (GSTT), and zeta (GSTZ)], which is a group of phase II enzymes that catalyze the glutathione conjugation of many endogenous and exogenous electrophilic compounds, such as environmental toxins, and oxidative stress products [2], [4]. The GSTM1, T1 and P1 enzymes are expressed in lung tissues [5], where the GSTP1 was found to be mainly present in the respiratory tract [6]. GSTP1 is found in humans with an A (Adenine) to G (Guanine) substitution at exon 5 causing Isoleucine (Ile) to Valine (Val) replacement at Cy5.5 hydrazide australia number 105 within the active site of the protein [7].
Aim of the work
Patients and methods This work was carried out on 30 patients with COPD diagnosed and classified according to GOLD 2013 [1], referred to the Chest Department, Faculty Of Medicine, Menoufia University and Chest hospital of Shebin El Kom. The study also included 20 healthy controls. Subjects were divided into:- After having a written consent; each patient underwent:Spirometry was done for all subjects. All patients had FEV1/FVC of less than 70% and post bronchodilator spirometry was performed after giving the patient a bronchodilator, such as an inhaled beta-agonist e.g. salbutamol 400μg) [1]. The following parameters were measured: The classification of Severity of Airflow Limitation in COPD patients with FEV1/FVC<0.70 (Based on Post-Bronchodilator FEV1) according to GOLD staging system (GOLD 2013) [1] into: 7 blood samples were drawn for studying glutathione S-transferase P1 gene polymorphism by PCR-RFLP. Blood collected on EDTA tubes was used for DNA extraction using gene JET whole blood DNA Mini Kits (Thermo Scientific, Sigma) stored at −20 for PCR amplification with an initial denaturation at 95 for 5min and repeated 40 cycles of denaturation at 95 for 1min, annealing at 56 for 1min and extension at 72 for 1min followed by a final extension at 72 for 5min using forward primer (5-GTAGTTTGCCCAAGGTCAAG-3) and reverse primer (5-AGCCACCTGAGGGGTAAG-3). PCR product was digested by fast digest AIw26I restriction enzyme for 2h at 37.
Results Table 1 shows the distribution of patients and controls regarding their demographic criteria: age, sex, smoking status, smoking index. The age of the studied patient ranged from 43 to 75years with mean age and standard deviation of 62.40±9.32 in group A, 59.66±6.33 in group B, 38.30±5.86 in group C and 40.40±7.73 in group D. Moreover, the number of male subjects was higher than females, 36 and 14, respectively. Regarding smoking status the number of current smokers was 14 and ex-smoker was 11, while non smokers were 25. Table 2 shows the comparison between the studied groups regarding their spirometric results, it shows the distribution of the studied groups regarding GOLD stages of patients in groups A and B (classified according to GOLD 2013). There were: 10 (66.7%) smoker patients in group (A) and 11 (73.7%) non-smoker patients in group (B) had moderate COPD. 5 (33.3%) smoker patients in group (A) had severe COPD. While from non-smoker patients in group (B) was 4 (26.7%) with severe COPD. There was a non significant difference between the studied groups (A) and (B) as regards the GOLD stage (P-value>0.05). Regarding the control groups C and D there were two subjects (20%) of group C (control smokers) having small airway obstruction and 8 (80%) normal, while those from non-smoker controls in group (D) were 10 (100%) with normal pulmonary function tests. There was a non significant difference between the studied groups (C) and (D) as regards to their pulmonary function tests (P-value>0.05).