Genetic polymorphism of epoxide hydrolase and glutathione S-transferase in COPD

Genetic susceptibility to the development of chronic obstructive pulmonary disease (COPD) might depend on variation in the activities of enzymes that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEPHX) and glutathione S-transferase (GST). It was investigated whether polymorphisms in these genes had any association with susceptibility to COPD and COPD severity. The genotypes of 184 patients with COPD and 212 control subjects were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the mEPHX, GSTM1, GSTT1 and GSTP1 genes. All subjects were smokers or exsmokers. The proportion of GSTM1-null genotypes was significantly higher in patients with COPD than in control subjects (61.4 versus 42.5%). No differences were observed in the frequency of polymorphic genotypes for mEPHX, GSTT1 and GSTP1. During combined analysis of genetic polymorphisms for mEPHX, GSTM1 and GSTP1, it was found that there are strong indicators for susceptibility to COPD (genotype combination with at least one mutant mEPHX exon‐3 allele (histidine 113), GSTM1 null and homozygous for the GSTP1 isoleucine 105 allele). The frequencies of homozygous mutant alleles of mEPHX exon 3 and the GSTM1-null genotype were significantly higher in patients with severe COPD (forced expiratory volume in one second of <35% of the predicted value). It is proposed that the combination of genetic variants including at least one mutant microsomal epoxide hydrolase exon‐3 allele and glutathione S-transferase M1-null and homozygous isoleucine 105 glutathione S-transferase P1 genotypes are significant indicators of susceptibility to chronic obstructive pulmonary disease in the Taiwanese population. In addition, the homozygous variant of microsomal epoxide hydrolase exon 3 and the glutathione S-transferase M1-null genotype are independent risk factors for developing severe chronic obstructive pulmonary disease.

[1]  A. Sandford,et al.  Genetic risk factors for chronic obstructive pulmonary disease. , 2002, Clinics in chest medicine.

[2]  N. Hizawa,et al.  Gene polymorphism for microsomal epoxide hydrolase and susceptibility to emphysema in a Japanese population. , 2000, The European respiratory journal.

[3]  J. Yim,et al.  Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1 , 2000, Thorax.

[4]  Y. Ouchi,et al.  Glutathione S-transferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease , 1999, Thorax.

[5]  D. Levy,et al.  Segregation analysis of pulmonary function among families in the Framingham Study. , 1998, American journal of respiratory and critical care medicine.

[6]  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.

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

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

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

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

[11]  P. Mahendra.  Increased risk for myelodysplastic syndrome in individuals with glutathione transferase theta 1 gene (GSTT1) defect , 1996 .

[12]  C. Bloomfield,et al.  Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect , 1996, The Lancet.

[13]  J. Broome,et al.  Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase (GSTT1 and GSTM1) and cytochrome P-450 (CYP2D6) loci. , 1995, Cancer research.

[14]  G. Chenevix-Trench,et al.  Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset. , 1995, Carcinogenesis.

[15]  M. Spitz,et al.  Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta. , 1995, Carcinogenesis.

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

[17]  C. Hassett,et al.  The human microsomal epoxide hydrolase gene (EPHX1): complete nucleotide sequence and structural characterization. , 1994, Genomics.

[18]  J. S. Sidhu,et al.  Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. , 1994, Human molecular genetics.

[19]  Jack A. Taylor,et al.  Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. , 1993, Journal of the National Cancer Institute.

[20]  H Vainio,et al.  The GSTM1 null genotype as a potential risk modifier for squamous cell carcinoma of the lung. , 1993, Carcinogenesis.

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

[22]  A. Buist,et al.  Correlates of FEV1 and prevalence of pulmonary conditions in Japanese-American men. , 1988, The American review of respiratory disease.

[23]  O. Mcbride,et al.  Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, complementary DNA-directed expression in COS-1 cells, and chromosomal localization. , 1988, The Journal of biological chemistry.

[24]  R. Pero,et al.  A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. , 1986, Carcinogenesis.

[25]  H. Glatt,et al.  The apparent ubiquity of epoxide hydratase in rat organs. , 1977, Biochemical pharmacology.

[26]  L. F. Black,et al.  Alpha1-antitrypsin and its deficiency. , 1974, The American review of respiratory disease.

[27]  F. Oesch,et al.  Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. , 1973, Xenobiotica; the fate of foreign compounds in biological systems.

[28]  N. Anthonisen,et al.  Susceptibility genes for rapid decline of lung function in the lung health study. , 2001, American journal of respiratory and critical care medicine.

[29]  M. Yamakido,et al.  Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese. , 2000, International journal of molecular medicine.

[30]  B. Make,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

[31]  M. Wu.  Study on maximal expiratory flow and volume in Chinese. I. Normal nonsmoking adults. , 1981, Taiwan yi xue hui za zhi. Journal of the Formosan Medical Association.

[32]  Wu Mc.  Study on maximal expiratory flow and volume in Chinese. I. Normal nonsmoking adults. , 1981 .