Glutathione S-transferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease

BACKGROUND Enzymes that contribute to the local detoxification in alveoli and bronchioles have an important role in the defence mechanism against tobacco smoke. It has been suggested that genetic susceptibility to smoking injury may confer a risk for the development of chronic obstructive pulmonary disease (COPD). The polymorphisms in glutathione S-transferase P1 (GSTP1), a xenobiotic metabolising enzyme, were investigated in patients with COPD. METHODS Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype GSTP1 polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val). Blood samples were taken from 53 patients with COPD and 50 control subjects at the Tokyo University Hospital, the Juntendo University Hospital, and the Tokyo Kenbikyoin Clinic for use in the study. RESULTS The proportion of GSTP1/Ile105 homozygotes was significantly higher in the patients with COPD than in the control subjects (79% vs 52%). The odds ratio for GSTP1/Ile105 homozygotes versus all other genotypes was 3.5 (95% CI 2.7 to 4.6) for COPD. Polymorphism at residue 114 of GSTP1 was not found in either group. CONCLUSIONS Genetic polymorphism of exon 5 of GSTP1 may be associated with COPD because the GSTP1/Ile105 genotype is predominantly found in COPD. It is suggested that the GSTP1/Ile105 genotype may be less protective against xenobiotics in tobacco smoke.

[1]  B Rosner,et al.  Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. , 1998, American journal of respiratory and critical care medicine.

[2]  P. Jemth,et al.  Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases. , 1998, The Biochemical journal.

[3]  B. Mannervik,et al.  Structure-activity relationships and thermal stability of human glutathione transferase P1-1 governed by the H-site residue 105. , 1998, Journal of molecular biology.

[4]  A. Seidel,et al.  Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons. , 1998, Carcinogenesis.

[5]  M. Juchau,et al.  Inhibition of embryonic retinoic acid synthesis by aldehydes of lipid peroxidation and prevention of inhibition by reduced glutathione and glutathione S-transferases. , 1998, Free radical biology & medicine.

[6]  G. B. Smith,et al.  Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. , 1998, Carcinogenesis.

[7]  F. Ali-Osman,et al.  Genomic Cloning of hGSTP1*C, an Allelic Human Pi Class Glutathione S-Transferase Gene Variant and Functional Characterization of Its Retinoic Acid Response Elements* , 1997, The Journal of Biological Chemistry.

[8]  Song-Lih Huang,et al.  Tumor Necrosis Factor- α Gene Polymorphism in Chronic Bronchitis , 1997 .

[9]  D. Harrison,et al.  Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema , 1997, The Lancet.

[10]  P. Barnes,et al.  Exhaled and nasal nitric oxide measurements: recommendations. The European Respiratory Society Task Force. , 1997, The European respiratory journal.

[11]  L. Harries,et al.  Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. , 1997, Carcinogenesis.

[12]  D. Lamb,et al.  Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer , 1997, Human & experimental toxicology.

[13]  D. Massaro,et al.  Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats , 1997, Nature Medicine.

[14]  D Hoffmann,et al.  The changing cigarette, 1950-1995. , 1997, Journal of toxicology and environmental health.

[15]  C. Su,et al.  Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis. , 1997, American journal of respiratory and critical care medicine.

[16]  Alan D. Lopez,et al.  Evidence-Based Health Policy--Lessons from the Global Burden of Disease Study , 1996, Science.

[17]  C. Smith,et al.  Association between the CYP1A1 gene polymorphism and susceptibility to emphysema and lung cancer , 1995, Clinical molecular pathology.

[18]  J C Yernault,et al.  Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. , 1995, The European respiratory journal.

[19]  C. Smith,et al.  Heterogeneous expression and polymorphic genotype of glutathione S-transferases in human lung. , 1994, Thorax.

[20]  R. Bascom Differential susceptibility to tobacco smoke: possible mechanisms. , 1991, Pharmacogenetics.

[21]  P. Board,et al.  Isolation of a cDNA clone and localization of the human glutathione S‐transferase 3 genes to chromosome bands 11q13 and 12q13‐14 , 1989, Annals of human genetics.

[22]  B. Mannervik The isoenzymes of glutathione transferase. , 2006, Advances in enzymology and related areas of molecular biology.

[23]  William A. Pryor,et al.  The Tar Radical ( s ) in Cigarette Smoke : ESR Studies , 2006 .

[24]  N. Pride,et al.  Definitions of emphysema, chronic bronchitis, asthma, and airflow obstruction: 25 years on from the Ciba symposium. , 1984, Thorax.

[25]  J. Hoidal,et al.  Potential mechanism of emphysema: alpha 1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Peto,et al.  The natural history of chronic airflow obstruction. , 1977, British medical journal.