Related Experiment Video
Updated: Jul 14, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Genetic polymorphisms of GSTP1 and mEPHX correlate with oxidative stress markers and lung function in COPD
Arpana Vibhuti1, Ehtesham Arif, Desh Deepak
1Functional Genomics Unit, Institute of Genomics and Integrative Biology, New Delhi, India.
Abstract:
The genetic susceptibility to COPD might depend on variations in detoxification enzymes that activate and detoxify cigarette smoke products, which otherwise generate oxidative stress causing pathogenesis. In a case-control study of 202 COPD patients and 136 normals, we examined the association of polymorphisms I105V, A114V of GSTP1 and Y113H, H139R of mEPHX individually or in combination with disease and their contribution to oxidative stress markers such as MDA, GSH, GPx and airflow obstruction. Patients were over-represented by the alleles 105V, 114V of GSTP1 and 113H, 139H of mEPHX (chi(2)=10.63, p=0.001, chi(2)=13.92, p<0.001, chi(2)=13.02, p<0.001 and chi(2)=4.48, p=0.034, respectively) and the haplotypes of same alleles i.e. 105V-114V and 113H-139H (chi(2)=14.58, p<0.001 and chi(2)=23.14, p<0.001). Moreover, there was marked over-representation of combination of genotypes, I105I+A114A of GSTP1 (53% vs. 36%) in controls; whereas, the combinations with 105V/114V alleles (64% vs. 47%) of GSTP1 (OR=1.99; 95% CI=1.28-3.09; p=0.002) and the homozygotes H113H+H139H (27% vs.10%) of mEPHX (OR=3.26; 95% CI=1.73-6.15; p=0.0001) in patients. Patients had significantly elevated MDA level (p<0.001) and decreased GSH level (p<0.001) and GPx activity (p=0.035), respectively. Of note, the genotypes, I105V/V105V, A114V/V114V of GSTP1 and Y113H/H113H of mEPHX associated with increased MDA level (p=0.04, p=0.03 and p=0.003), decreased GSH level (p=0.019, p=0.007 and p=0.0006) and lower FEV1 (p=0.23, p=0.037 and p=0.029), respectively, in patients; so was the correlation of these biomarkers and lung function with the combinations of the genotypes. In conclusion, 105V/114V alleles of GSTP1 and 113H/139H alleles of mEPHX and the combination of genotypes with same alleles associated with imbalanced oxidative stress and lung function in patients, signifying the importance in the disease.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features