Combined Analysis of EPHX1, GSTP1, GSTM1 and GSTT1 Gene Polymorphisms in Relation to Chronic Obstructive Pulmonary Disease Risk and Lung Function Impairment

Abstract

Abstract.Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD). Nevertheless, a minority of chronic heavy cigarette smokers develops COPD. This suggests important contribution of other factors such as genetic predisposing. Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment. Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia. Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR. Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR = 4.07) and null-GSTM1/105Val/Val GSTP1 (OR = 3.56) genotypes with increased risk of COPD (respectively P = 0.0094 and P = 0.0153). The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P = 0.01; P = 0.009; P = 0.008 and P = 0.001). Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of ΔFEV1 in patients (P = 0.028). In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function.

The Cumulative Effect of Gene–Gene Interactions Between GSTM1, CHRNA3, CHRNA5 and SOD3 Gene Polymorphisms Combined with Smoking on COPD Risk

“…GSTM1 , encoding Glutathione S Transferase Mu 1, is the protein class of the highly polymorphic, cytosolic and membrane bound glutathione S-transferase, of which the null variation has been linked to COPD and lung cancer, due to increased susceptibility to toxins and carcinogens. 10 , 19 Our result showed null deletion genotype showed high risk of COPD as described elsewhere. CHRNA3/CHRNA5 , encoding alpha 3 or 5 subunit of nicotinic acetylcholine receptor, more likely related to nicotine dependence of smoking.…”

Exploring the interaction among EPHX1, GSTP1, SERPINE2, and TGFB1 contributing to the quantitative traits of chronic obstructive pulmonary disease in Chinese Han population

“…Up to now, although there are many different candidate genes which have been investigated for their potential roles in lung function impairment in smokers [ 17 , 18 ], few works were interested to study the combinations of polymorphisms in COPD quantitative traits. In this paper, our study tested for the association of genetic interaction with seven COPD-related quantitative traits using recently developed GMDR and QMDR algorithms.…”

“…Interestingly, we found EPHX1 interact with GSTP1 directly for FEV 1 trait for COPD patients, which is consistent with the interaction identified by GeneMANIA. In previous studies, Lakhdara et al have suggested that combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function based on the analysis for Tunisian population [ 18 ]. Salam et al found that EPHX1 and GSTP1 variants contribute to the occurrence of childhood asthma and increase asthma susceptibility to exposures from major roads based on the analysis for white children in Southern California [ 19 ].…”

Early Origins of Chronic Obstructive Pulmonary Disease: Prenatal and Early Life Risk Factors

“…The interaction between ADAM33 and smoking exposure seems to be associated with a higher risk of impaired lung function and asthma development by age 8 [21,22]. Genes involved in metabolism and the clearance of endogenous products derived from oxidative stress such as EPHX1, CYP1A1, and GSTT1 can modify the impact of smoke and air pollutant exposure (PM 2.5 and polycyclic aromatic hydrocarbons) on respiratory exacerbations and seem to be related to the development of emphysema and COPD later in life [23][24][25][26].…”