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

Ramzi Lakhdar,Houria Daimi,Jemni Ben Chibani,Gérard Lefranc,Amel Haj Khelil,Mohsen Hassine,Jalel Knani,Nadia Leban,Sabri Denden

doi:10.1155/2011/956250

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.

Highlights

Chronic obstructive pulmonary disease (COPD) is a devastating clinical problem and is a major cause of ill health increasing in many parts of the world
In crude combined analysis of EPHX1, GSTP1, GS TM1 and GSTT1 gene polymorphisms, our results demonstrated that combined 113His/His EPHX1/nullGSTM1, null-GSTM1/105Val/Val GSTP1 and 113His/ His EPHX1/105Val/Val GSTP1 genotypes were associated with significantly increased risk of COPD
Our results showed that null-GSTM1/null-GSTT1 (OR = 1.66; confidence intervals (CI): 0.95–2.9; P = 0.072), 105Val/Val GSTP1/null GSTT1 (OR = 2.51; CI: 0.97–6.5; P = 0.052) and 113His/His EPHX1/null GSTT1 genotypes (OR = 2.68; CI: 0.93– 7.68; P = 0.058) were not related to COPD

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a devastating clinical problem and is a major cause of ill health increasing in many parts of the world. Despite that the most important risk factor for the development of COPD is cigarette smoking, it has been estimated that only 10–20% of chronic heavy smokers will ever develop symptomatic COPD, which indicates an additional genetic or environmental contribution [2,3]. GlutathioneS-transferases (GSTM1, T1 and P1) and microsomal epoxide hydrolase (EPHX1) were previously studied in relationship with COPD [6,7,8,9,10,11,12,13,14]

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