Genetic predisposition is one of the causes of Chronic Obstructive Pulmonary Disease (COPD). This study is designed to investigate effect of the activity of an important antioxidant enzyme heme oxygenase-1 (HOX-1) by (GT)n dinucleotide repeat (GT)n ≤ 26 S allel, 27≤(GT)n≤ 31 M allel, (GT)n ≥ 32 L (long) allel), levels of serum iron and bilirubin, the last products of enzyme, on severity of COPD and exacerbations of disease. Three different staged 90 COPD patients and 93 controls were included. By increasing the severity of disease, bilirubin levels were coming closer to the lower limit within normal range. Iron levels of Group 2 (moderate) and 3 (severe) were significantly lower than Group 1 (mild), (p=0,025, p=0,035). There was an inversely related statistically significant correlation between exacerbation numbers and iron (p=0,016). Allel frequency and carrier of L ((GT)n ≥ 32) allel were similar between patient and control group, and patient group in its own (p=0,458, p=0,445). There was no significant relation between individuals with L allel (SL, ML, LL) and without L allel (SS, SM, MM) according to levels of iron and bilirubin, number of exacerbations and FEV1 (p=0,631, p=0,065, p=0,356). In conclusion; by the progression of COPD, levels of bilirubin and iron are liable to decrease while the number of exacerbations is increasing. (GT)n polymorphism of COPD patients in the study group is not a risk factor for development and stage of disease, frequent exacerbation, low iron and bilirubin levels
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1. Shibahara S. The heme oxygenase dilemma in cellular homeostasis: new insights for the feedback regulation of heme catabolism. Thoku J. Exp. Med. 200,167-186, 2003.
2. Delic J, Onclecq R, Moisan-Coppey M. Inhibition and enhancement of eukaryotic gene expression by potential non-B DNA sequences. Biochem. Biophys. Res. Commun 1991; 181: 818-826.
3. Yamada N, Yamaya M, Okinaga S et al. Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am. J. Hum. Genet 2000; 66: 187-195.
4. Otterbein LE, Kolls JK, Mantell L, et al. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J. Clin. Invest 1999; 103: 1047-1054.
5. Fu WP, Zhao Z, Fang LZ et al. Heme oxygenase-1 polymorphism associated with severity of chronic obstructive pulmonary disease. Chinese Medical Journal 2007; 120: 12-16.
6. Guénégou A, Leynaert B, Bénessiano J et al. Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample. Results from the European Community Respiratory Health Survey (ECRHS), France J Med Genet 2006; 43: 43.
7. He JQ, Ruan J, Connett JE et al. Antioxidant Gene Polymorphisms and Susceptibility to a Rapid Decline in Lung Function in Smokers. Am J Respir Crit Care Med 2002; 166: 323- 328.
8. Yamashita K, McDaid J, Öllinger R, Tsui TY, Berberat PO, Usheva A, Csizmadia E, Smith RN, Soares MP, Bach FH. Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts. FASEB J. 18, 765–767, 2004.
9. Sarady-Andrews JK, Liu F, Gallo D et al. Biliverdin administration protects against endotoxin-induced acute lung injury in rats. Am. J. Physiol. Lung Cell. Mol. Physiol 2005; 289: 1131-1137.
10. Soares MP, Seldon MP, Gregoire IP et al. Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J Immunol 2004; 172: 3553-3563.
11. Kaneda H, Ohno M, Taguchi J et al. Heme oxygenase-1 gene promoter polymorphism is associated with coronary artery disease in Japanese patients with coronary risk factors. Arterioscler Thromb Vasc Biol 2002; 22: 1680-1685.
12. Chen YH, Lin SJ, Lin MW, Tsai HL, Kuo SS, Chen JW, Charng MJ, Wu TC, Chen LC, Ding YA, Pan WH, Jou YS, Chau LY: Microsatellite polymorphism in promoter of heme oxygenase-1 gene is associated with susceptibility to coronary artery disease in type 2 diabetic patients. Hum Genet 111:1– 8, 2002.
13. Novotny L, Vitek L. Inverse relationship between serum bilirubin and atherosclerosis in men: a meta-analysis of published studies. Exp. Biol. Med. (Maywood) 228, 568–571, 2003.
14. Brown KE, Sin DD, Voelker H, Connett JE, Niewoehner1 DE, Kunisaki KM et al. Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations Respiratory Research 18:179, 2017.
15. Apperley S, Park HY, Holmes DT, Man S. F. P, Tashkin D, Wise RA Serum Bilirubin and Disease Progression in Mild COPD CHEST 2015; 148 (1): 169 – 175.
16. Karadag F, Cildag O, Altinisik M, Kozaci LD, Kiter G, Altun C. Trace elements as a component of oxidative stress in COPD Respirology 2004; 9: 33-37.
17. McKeever TM, Lewis SA, Smit HA et al .A multivariate analysis of serum nutrient levels and lung function Respir Res 2008; 29: 67