The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.
1. Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013, http://www.goldcopd.org/guidelines-global-strategy--for-diagnosis-management.html; last access date October 5, 2013.
2. B. Lamprecht, M. A. McBurnie, W. M. Vollmer, G. Gudmundsson, T. Welte, E. Nizankowska- -Mogilnicka, M. Studnicka, E. Bateman, J. M. Anto, P. Burney, D. M. Mannino and S. A. Buist (BOLD Collaborative Research Group), COPD in never smokers: results from the population- -based burden of obstructive lung disease study, Chest 139 (2011) 752-763; DOI: 10.1378/chest. 10-1253.
3. R. Lakhdar, S. Denden, A. Kassab, N. Leban, J. Knani, G. Lefranc, A. Miled, J. B. Chibani and A. H. Khelil, Update in chronic obstructive pulmonary disease: role of antioxidant and metabolizing gene polymorphisms, Exp. Lung. Res. 37 (2011) 364-375; DOI: 10.3109/01902148.2011. 580416.
4. R. C. Strange, M. A. Spiteri, S. Ramachandran and A. A. Fryer, Glutathione-S-transferase family of enzymes, Mutat. Res. 482 (2001) 21-26.
5. J. D. Hayes, J. U. Flanagan and I. R. Jowsey, Glutathione transferases, Annu. Rev. Pharmacol. Toxicol. 45 (2005) 51-88; DOI: 10.1146/annurev.pharmtox.45.120403.095857.
6. J. D. Hayes and D. J. Pulford, The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance, Crit. Rev. Biochem. Mol. Biol. 30 (1995) 445-600.
7. K. Sundberg, A. S. Johansson, G. Stenberg, M. Widersten, A. Seidel, B. Mannervik and B. Jernström, Differences in catalytic efficiency of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons, Carcinogenesis 19 (1998) 433-436.
8. D. J. Harrison, A. M. Cantlay, F. Rae, D. Lamb and C. A. Smith, Frequency of glutathione S- -transferase M1 deletion in smokers with emphysema and lung cancer, Hum. Exp. Toxicol. 16 (1997) 356-360.
9. S. L. Cheng, C. J. Yu, C. J. Chen and P. C. Yang, Genetic polymorphisms of epoxide hydrolase and glutathione S-transferase in COPD, Eur. Respir. J. 23 (2004) 818-824; DOI: 10.1183/ 09031936.04.00104904.
10. J. J. Yim, G. Y. Park, C. T. Lee, Y. W. Kim, S. K. Han, Y. S. Shim and C. G. Yoo, 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, Thorax 55 (2002) 121-125; DOI: 10.1136/thorax.55.2.121.
11. J. Q. He, J. Ruan, J. E. Connett, N. R. Anthonisen, P. D. Pare and A. J. Sandford, Antioxidant polymorphisms and susceptibility to a rapid decline in lung function in smokers, Am. J. Res. Crit. Care. Med. 166 (2002) 323-328; DOI: 10.1164/rccm.2111059.
12. T. Ishii, T. Matsuse, S. Teramoto, H. Matsui, M. Miyao, T. Hosoi, H. Takahashi, Y. Fukuchi and Y. Ouchi, Glutathione S-transferase P1 (GSTP1) polymorphism in patient with chronic obstructive pulmonary disease, Thorax 54 (1999) 693-696; DOI: 10.1136/thx.54.8.693.
13. J. J. Yim, C. G. Yoo, C. T. Lee, Y. W. Kim, S. K. Han and Y. S. Shim, Lack of association between glutathione S-transferase P1 polymorphism and COPD in Koreans, Lung 180 (2002) 119-125; DOI: 1007/s004080000086.
14. F. Rodriguez, C. De La Roza, R. Jardi, M. Schaper, R. Vidal R and M. Miravitlles, Glutathione S-transferase P1 and lung function in patients with alpha(1)-antitrypsin deficiency and COPD, Chest 127 (2005) 1537-1543; DOI: 10.1378/chest.127.5.1537.
15. V. R. Arruda, C. E. Grignolli, M. S. Gonqalves, M. C. Soares, R. Menezes, S. T. Saad and F. F. Costa, Prevalence of homozygosity for the deleted alleles of glutathione S-transferase mu (GSTM1) and theta (GSTT1) among distinct ethnic groups from Brazil: relevance to environmental carcinogenesis?, Clin. Genet. 54 (1998) 210-214.
16. S. L. Zhong, S. F. Zhou, X. Chen, X. Chan, S. Y. Chan, E. Chan, K. Y. Ng,W.Duan andM. Huang, Relationship between genotype and enzyme activity of glutathione S-transferase M1 and P1 in Chinese, Eur. J. Pharm. Sci. 28 (2006) 77-85; DOI: 10.1016/j.ejps.2006.01.002.
17. M. Chan-Yeung, S. P. Ho, A. H. Cheung, L. K. So, P. C.Wong, K. K. Chan, J.W. Chan, M. S. Ip and J. C. Mak, Polymorphisms of glutathione S-transferase genes and functional activity in smokers with or without COPD, Int. J. Tuberc. Lung. Dis. 11 (2007) 508-514.
18. J. G. Gea, M. Pasto, M. A. Carmona, M. Orozco-Levi, J. Palomeque and J. Broquetas, Metabolic characteristics of the deltoid muscle in patients with chronic obstructive pulmonary disease, Eur. Respir. J. 17 (2001) 939-945.
19. S. A. Miller, D. D. Dykes and H. F. Polesky, A simple salting out procedure for extracting DNA from human nucleated cells, Nucleic. Acids. Res. 16 (1988) 1215.
20. M. Habdous, M. Vincent-Viry, S. Visvikis and G. Siest, Rapid spectrophotometric method for serum glutathione S-transferase activity, Clin. Chim. Acta 326 (2002) 131-142; DOI: 10.1016/S0009- -8981(02)00329-7.
21. S. T. Saarikoski, A. Voho, M. Reinikainen, S. Anttila, A. Karjalainen, C. Malaveille, H. Vainio, K. Husrafvel-Pursiainen and A. Hirvonen, Combined effect of polymorphic GST genes on individual susceptibility to lung cancer, Int. J. Cancer. 77 (1998) 516-521.
22. I. Žuntar, S. Kalanj-Bognar, E. Topi}, R. Petlevski, M. [tefanovi} and V. Demarin, The glutathione S-transferase polymorphisms in a control population and in Alzheimer’s disease patients, Clin. Chem. Lab. Med. 42 (2004) 334-339; DOI: 10.1515/CCLM.2004.059.
23. A. T. Hill, E. J. Campbell, A. M. Ward and R. A. Stockley, Chronic obstructive pulmonary disease, with and without alpha-1-antitrypsin deficiency: management practices in the U.K., Respir. Med. 93 (1999) 481-490; DOI: 10.1016/S0954-6111(99)90091-4.
24. I. Čepelak, S. Dodig, D. Romi}, N. Ruljancic, S. Popovic-Grle and A. Mali}, Enzyme catalytic activities in chronic obstructive pulmonary disease, Arch. Med. Res. 37 (2006) 624-629; DOI: 10.1016/ j.arcmed.2006.01.004.
25. R. Lakhdar, S. Denden, J. Knani, N. Leban, H. Daimi, M. Hassine, G. Lefranc, J. Ben Chibani and A. Haj Khelil, Relationship between glutathione S-transferase P1 polymorphisms and chronic obstructive pulmonary disease in a Tunisian population, Genet. Mol. Res. 9 (2010) 897-907; DOI: 10.4238/vol9-2gmr770.
26. F. Yan, C. Chen, J. Jing, W. Li, H. Shen and X. Wang, Association between polymorphism of glutathione S-transferase P1 and chronic obstructive pulmonary disease: a meta-analysis, Respir. Med. 104 (2010) 473-480; DOI: 10.1016/j.rmed.2010.01.009.
27. J. Smolonska, C. Wijmenga, D. S. Postma and H. M. Boezen, Erratum: Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years’ research, Am. J. Respir. Crit. Care. Med. 181 (2010) 765.
28. J. Smolonska, C. Wijmenga, D. S. Postma and H. M. Boezen, Meta-analyses on suspected chronic obstructive pulmonary disease genes: a summary of 20 years’ research, Am. J. Respir. Crit. Care. Med. 180 (2009) 618-631; DOI: 10.1164/rccm.200905-07220C.
29. M. Imboden, S. H. Downs, O. Senn, G.Matyas, O. Brändli, E.W. Russi, C. Schindler, U. Ackermann- Liebrich, W. Berger and N. M. Probst-Hensch, (Sapaldia Team), Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study, Resp. Res. 8 (2007) 2-17; DOI: 10.1186/1465-9921-8-2.
30. J. Židzik, E. Slaba, P. Joppa, Z. Kluchova, P. Skyba, V. Habalova, J. Salagovic and R. Tka~ova, Glutathione S-transferase and microsomal epoxid hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population, Croat. Med. J. 49 (2008) 182-191; DOI: 10.3325/cmj.2008.2.182.
31. S. Mehrotra, A. Sharma, S. Kumar, S. Sardanaand J. K. Sharma, Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD, Int. J. Immunogen. 7 (2010) 263-267; DOI: 10.1111/ j.1744-313X.2010.00918.x.
32. C. Z. Chen, R. H. Wang, C. H. Lee, C. C. Lin, H. Y. Chang and T. R. Hsiue, Polymorphism of microsomal epoxide hydrolase is associated with chronic obstructive pulmonary disease and bronchodilator response, J. Med. Assoc. 110 (2011) 685-689; DOI: 10.1016/j.jfma.2011.09.003.
33. R. Lakhdar, S. Denden, M. H. Mouhamed, A. Chalgoum, N. Leban, J. Knani, G. Lefranc, A. Miled, J. Ben Chibani and A. H. Khelil, Correlation of EPHX1, GSTP1, GSTM1, and GSTT1 genetic polymorphisms with antioxidative stress markers in chronic obstructive pulmonary disease, Exp. Lung Res. 37 (2011) 195-204; DOI: 10.3109/01902148.2010.535093.
34. D. Sheehan, G. Meade, V. M. Foley and C. A. Dowd, Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily, Biochem. J. 360 (2001) 1-16; DOI: 10.1042/0264-6021:3600001.
35. A. R. Bentley, S. B. Kritchevsky, T. B. Harris, A. B. Newman, D. C. Bauer, B. Meibohm, A. G. Clark and P. A. Cassano, Genetic variation in antioxidant enzymes and lung function, Free. Radic. Biol. Med. 52 (2012) 1577-1583; DOI: 10.1016/j.freeradbiomed.2012.02.025.