Relationship between glutathione S-transferase P1 polymorphisms and chronic obstructive pulmonary disease in a Tunisian population

R. Lakhdar, S. Denden, J. Knani, N. Leban, H. Daimi, M. Hassine, G. Lefranc, J. Ben Chibani, A. Haj Khelil
Published May 11, 2010
Genet. Mol. Res. 9 (2): 897-907 (2010)
DOI 10.4238/vol9-2gmr770

About the Authors
R. Lakhdar, S. Denden, J. Knani, N. Leban, H. Daimi, M. Hassine, G. Lefranc, J. Ben Chibani, A. Haj Khelil

Corresponding author
R. Lakhdar


Chronic obstructive pulmonary disease (COPD) is a multifactorial disease with possible genetic predisposition and involvement of various environmental factors. Several candidate genes have been reported as potentially associated with this lung disease. The glutathione S-transferase P1 gene (GSTP1) was proposed to be involved in susceptibility to develop COPD. It belongs to the GST family, which is a group of phase II enzymes that catalyze the glutathione conjugation of many endogenous and exogenous electrophilic compounds, such as carcinogens, therapeutic drugs, environmental toxins, and oxidative stress products. We conducted a case-control study to investigate genetic polymorphisms of this enzyme [exon 5 (Ile105Val) and exon 6 (Ala114Val)] in 234 unrelated COPD cases and 182 healthy controls from a Tunisian population. Genotyping was carried out using polymerase chain reaction and restriction fragment length polymorphism methods. GSTP1 Ala114/Val114 and Val114/Val114 genotypes were not found in either patients or healthy controls. However, there were differences in the distribution of various exon 5 GSTP1 genotypes between COPD patients and healthy controls. GSTP1 Val105/Val105 was significantly more common in patients compared to controls (OR = 2.67; 95%CI = 1.45-4.92; P = 0.0013). Multivariate logistic regression analysis confirmed a significant relationship between the mutant genotype and COPD (OR = 2.58; 95%CI = 1.31-5.09; P = 0.026), after adjustment for classic risk factors. Analysis of variance showed no correlation between age, body-mass index, pack-years, percentage of predicted FEV1 values, and any of the GSTP1 genotypes. We conclude that subjects with GSTP1 Val105 allele are at higher risk of COPD.

Key words: Chronic obstructive pulmonary disease, Genetic polymorphism, Glutathione S-transferase.

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