Association between HO‑1 gene promoter polymorphisms and diseases (Review)

Ma,Lin-Lin; Sun,Lei; Wang,Yu-Xi; Sun,Bai-He; Li,Yan-Fei; Jin,Yue-Ling

doi:10.3892/mmr.2021.12545

Association between HO‑1 gene promoter polymorphisms and diseases (Review)

Authors:
- Lin-Lin Ma
- Lei Sun
- Yu-Xi Wang
- Bai-He Sun
- Yan-Fei Li
- Yue-Ling Jin
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Affiliations: School of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai 201318, P.R. China, Management Department of Scientific Research, Shanghai Science and Technology Museum, Shanghai 200127, P.R. China
Published online on: November 25, 2021 https://doi.org/10.3892/mmr.2021.12545
Article Number: 29
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Heme oxygenase‑1 (HO‑1) is an inducible cytoprotective enzyme that degrades heme into free iron, carbon monoxide and biliverdin, which is then rapidly converted into bilirubin. These degradation products serve an important role in the regulation of inflammation, oxidative stress and apoptosis. While the expression level of HO‑1 is typically low in most cells, it may be highly expressed when induced by a variety of stimulating factors, a process that contributes to the regulation of cell homeostasis. In the 5'‑non‑coding region of the HO‑1 gene, there are two polymorphic sites, namely the (GT)n dinucleotide and T(‑413)A single nucleotide polymorphism sites, which regulate the transcriptional activity of HO‑1. These polymorphisms have been shown to be closely associated with the occurrence and progression of numerous diseases, including cardiovascular, pulmonary, liver and kidney, various types of cancer and viral diseases. The present article reviews the progress that has been made in research on the association between the two types of polymorphisms and these diseases, which is expected to provide novel strategies for the diagnosis, treatment and prognosis of various diseases.

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1	Gozzelino R, Jeney V and Soares MP: Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 50:323–354. 2010. View Article : Google Scholar : PubMed/NCBI
2	Wagener FA, Volk HD, Willis D, Abraham NG, Soares MP, Adema GJ and Figdor CG: Different faces of the heme-heme oxygenase system in inflammation. Pharmacol Rev. 55:551–571. 2003. View Article : Google Scholar : PubMed/NCBI
3	Kim HP, Ryter SW and Choi AM: CO as a cellular signaling molecule. Annu Rev Pharmacol Toxicol. 46:411–449. 2006. View Article : Google Scholar : PubMed/NCBI
4	Calabrese V, Butterfield DA, Scapagnini G, Stella AG and Maines MD: Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: Relevance to brain aging, neurodegenerative disorders, and longevity. Antioxid Redox Signal. 8:444–477. 2006. View Article : Google Scholar : PubMed/NCBI
5	Exner M, Minar E, Wagner O and Schillinger M: The role of heme oxygenase-1 promoter polymorphisms in human disease. Free Radic Biol Med. 37:1097–1104. 2004. View Article : Google Scholar : PubMed/NCBI
6	Linnenbaum M, Busker M, Kraehling JR and Behrends S: Heme oxygenase isoforms differ in their subcellular trafficking during hypoxia and are differentially modulated by cytochrome P450 reductase. PLoS One. 7:e354832012. View Article : Google Scholar : PubMed/NCBI
7	Shibahara S: The heme oxygenase dilemma in cellular homeostasis: New insights for the feedback regulation of heme catabolism. Tohoku J Exp Med. 200:167–186. 2003. View Article : Google Scholar : PubMed/NCBI
8	Zhou J, Terluk MR, Basso L, Mishra UR, Orchard PJ, Cloyd JC, Schröder H and Kartha RV: N-acetylcysteine provides cytoprotection in murine oligodendrocytes through heme oxygenase-1 activity. Biomedicines. 8:2402020. View Article : Google Scholar : PubMed/NCBI
9	Jazwa A and Cuadrado A: Targeting heme oxygenase-1 for neuroprotection and neuroinflammation in neurodegenerative diseases. Curr Drug Targets. 11:1517–1531. 2010. View Article : Google Scholar : PubMed/NCBI
10	Seu L, Burt TD, Witte JS, Martin JN, Deeks SG and McCune JM: Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans. Genes Immun. 13:258–267. 2012. View Article : Google Scholar : PubMed/NCBI
11	Hirai H, Kubo H, Yamaya M, Nakayama K, Numasaki M, Kobayashi S, Suzuki S, Shibahara S and Sasaki H: Microsatellite polymorphism in heme oxygenase-1 gene promoter is associated with susceptibility to oxidant-induced apoptosis in lymphoblastoid cell lines. Blood. 102:1619–1621. 2003. View Article : Google Scholar : PubMed/NCBI
12	Rueda B, Oliver J, Robledo G, López-Nevot MA, Balsa A, Pascual-Salcedo D, González-Gay MA, González-Escribano MF and Martín J: HO-1 promoter polymorphism associated with rheumatoid arthritis. Arthritis Rheum. 56:3953–3958. 2007. View Article : Google Scholar : PubMed/NCBI
13	Brydun A, Watari Y, Yamamoto Y, Okuhara K, Teragawa H, Kono F, Chayama K, Oshima T and Ozono R: Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis. Hypertens Res. 30:341–348. 2007. View Article : Google Scholar : PubMed/NCBI
14	Loboda A, Damulewicz M, Pyza E, Jozkowicz A and Dulak J: Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism. Cell Mol Life Sci. 73:3221–3247. 2016. View Article : Google Scholar : PubMed/NCBI
15	Zhang DD: Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev. 38:769–789. 2006. View Article : Google Scholar : PubMed/NCBI
16	Jaramillo MC and Zhang DD: The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 27:2179–2191. 2013. View Article : Google Scholar : PubMed/NCBI
17	Motohashi H, Katsuoka F, Engel JD and Yamamoto M: Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Proc Natl Acad Sci USA. 101:6379–6384. 2004. View Article : Google Scholar : PubMed/NCBI
18	Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, et al: An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 236:313–322. 1997. View Article : Google Scholar : PubMed/NCBI
19	Dhakshinamoorthy S, Jain AK, Bloom DA and Jaiswal AK: Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H: Quinone oxidoreductase 1 gene expression and induction in response to antioxidants. J Biol Chem. 280:16891–16900. 2005. View Article : Google Scholar : PubMed/NCBI
20	Reichard JF, Motz GT and Puga A: Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1. Nucleic Acids Res. 35:7074–7086. 2007. View Article : Google Scholar : PubMed/NCBI
21	Medina MV, Sapochnik D, Garcia Solá M and Coso O: Regulation of the expression of heme oxygenase-1: Signal transduction, gene promoter activation, and beyond. Antioxid Redox Signal. 32:1033–1044. 2020. View Article : Google Scholar : PubMed/NCBI
22	Alam J and Cook JL: How many transcription factors does it take to turn on the heme oxygenase-1 gene? Am J Respir Cell Mol Biol. 36:166–174. 2007. View Article : Google Scholar : PubMed/NCBI
23	Dawn B and Bolli R: HO-1 induction by HIF-1: A new mechanism for delayed cardioprotection? Am J Physiol Heart Circ Physiol. 289:H522–H524. 2005. View Article : Google Scholar : PubMed/NCBI
24	Li X, Yu J, Gong L, Zhang Y, Dong S, Shi J, Li C, Li Y, Zhang Y and Li H: Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway. Free Radic Biol Med. 165:243–253. 2021. View Article : Google Scholar : PubMed/NCBI
25	Tong Y, Kai J, Wang S, Yu Y, Xie S, Zheng H, Wang Y, Liu Y, Zhu K, Guan X, et al: VHL regulates the sensitivity of clear cell renal cell carcinoma to SIRT4-mediated metabolic stress via HIF-1α/HO-1 pathway. Cell Death Dis. 12:6212021. View Article : Google Scholar : PubMed/NCBI
26	He C, Zhang W, Li S, Ruan W, Xu J and Xiao F: Edaravone improves septic cardiac function by inducing an HIF-1α/HO-1 pathway. Oxid Med Cell Longev. 2018:52163832018. View Article : Google Scholar : PubMed/NCBI
27	Lee PJ, Jiang B-H, Chin BY, Iyer NV, Alam J, Semenza GL and Choi AK: Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem. 272:5375–5381. 1997. View Article : Google Scholar : PubMed/NCBI
28	Tanos T, Marinissen MJ, Leskow FC, Hochbaum D, Martinetto H, Gutkind JS and Coso OA: Phosphorylation of c-Fos by members of the p38 MAPK family. Role in the AP-1 response to UV light. J Biol Chem. 280:18842–18852. 2005. View Article : Google Scholar : PubMed/NCBI
29	Monje P, Marinissen MJ and Gutkind JS: Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor. Mol Cell Biol. 23:7030–7043. 2003. View Article : Google Scholar : PubMed/NCBI
30	McBride K and Nemer M: The C-terminal domain of c-fos is required for activation of an AP-1 site specific for jun-fos heterodimers. Mol Cell Biol. 18:5073–5081. 1998. View Article : Google Scholar : PubMed/NCBI
31	Yeh CH, Chen TP, Wang YC, Lin YM and Lin PJ: HO-1 activation can attenuate cardiomyocytic apoptosis via inhibition of NF-kappaB and AP-1 translocation following cardiac global ischemia and reperfusion. J Surg Res. 155:147–156. 2009. View Article : Google Scholar : PubMed/NCBI
32	Lee PJ, Camhi SL, Chin BY, Alam J and Choi AM: AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1. Am J Physiol Lung Cell Mol Physiol. 279:L175–L182. 2000. View Article : Google Scholar : PubMed/NCBI
33	Paine A, Eiz-Vesper B, Blasczyk R and Immenschuh S: Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol. 80:1895–1903. 2010. View Article : Google Scholar : PubMed/NCBI
34	Campbell NK, Fitzgerald HK and Dunne A: Regulation of inflammation by the antioxidant haem oxygenase 1. Nat Rev Immunol. 21:411–425. 2021. View Article : Google Scholar : PubMed/NCBI
35	Merecz-Sadowska A, Sitarek P, Kucharska E, Kowalczyk T, Zajdel K, Cegliński T and Zajdel R: Antioxidant properties of plant-derived phenolic compounds and their effect on skin fibroblast cells. Antioxidants (Basel). 10:7262021. View Article : Google Scholar : PubMed/NCBI
36	Yarmohammadi F, Hayes AW and Karimi G: Natural compounds against cytotoxic drug-induced cardiotoxicity: A review on the involvement of PI3K/Akt signaling pathway. J Biochem Mol Toxicol. 35:e226832021. View Article : Google Scholar : PubMed/NCBI
37	Zhou Y, Jiang Z, Lu H, Xu Z, Tong R, Shi J and Jia G: Recent advances of natural polyphenols activators for Keap1-Nrf2 signaling pathway. Chem Biodivers. 16:e19004002019. View Article : Google Scholar : PubMed/NCBI
38	Zhang H, Liu YY, Jiang Q, Li KR, Zhao YX, Cao C and Yao J: Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling. Free Radic Biol Med. 69:219–228. 2014. View Article : Google Scholar : PubMed/NCBI
39	Zhang HF, Wang JH, Wang YL, Gao C, Gu YT, Huang J, Wang JH and Zhang Z: Salvianolic acid A protects the kidney against oxidative stress by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway in 5/6 nephrectomized rats. Oxid Med Cell Longev. 2019:28535342019.PubMed/NCBI
40	Gu X, Zheng C, Zheng Q, Chen S, Li W, Shang Z and Zhang H: Salvianolic acid A attenuates early brain injury after subarachnoid hemorrhage in rats by regulating ERK/P38/Nrf2 signaling. Am J Transl Res. 9:5643–5652. 2017.PubMed/NCBI
41	Sun GY, Chen Z, Jasmer KJ, Chuang DY, Gu Z, Hannink M and Simonyi A: Quercetin attenuates inflammatory responses in BV-2 microglial cells: Role of MAPKs on the Nrf2 pathway and induction of heme oxygenase-1. PLoS One. 10:e01415092015. View Article : Google Scholar : PubMed/NCBI
42	Yao P, Nussler A, Liu L, Hao L, Song F, Schirmeier A and Nussler N: Quercetin protects human hepatocytes from ethanol-derived oxidative stress by inducing heme oxygenase-1 via the MAPK/Nrf2 pathways. J Hepatol. 47:253–261. 2007. View Article : Google Scholar : PubMed/NCBI
43	Campbell NK, Fitzgerald HK, Fletcher JM and Dunne A: Plant-derived polyphenols modulate human dendritic cell metabolism and immune function via AMPK-dependent induction of heme oxygenase-1. Front Immunol. 10:3452019. View Article : Google Scholar : PubMed/NCBI
44	Kosuru R, Kandula V, Rai U, Prakash S, Xia Z and Singh S: Pterostilbene decreases cardiac oxidative stress and inflammation via activation of AMPK/Nrf2/HO-1 pathway in fructose-fed diabetic rats. Cardiovasc Drugs Ther. 32:147–163. 2018. View Article : Google Scholar : PubMed/NCBI
45	Nakasone R, Ashina M, Abe S, Tanimura K, Van Rostenberghe H and Fujioka K: The role of heme oxygenase-1 promoter polymorphisms in perinatal disease. Int J Environ Res Public Health. 18:35202021. View Article : Google Scholar : PubMed/NCBI
46	Öllinger R and Pratschke J: Role of heme oxygenase-1 in transplantation. Transpl Int. 23:1071–1081. 2010. View Article : Google Scholar : PubMed/NCBI
47	Schulz S, Chisholm KM, Zhao H, Kalish F, Yang Y, Wong RJ and Stevenson DK: Heme oxygenase-1 confers protection and alters T-cell populations in a mouse model of neonatal intestinal inflammation. Pediatr Res. 77:640–648. 2015. View Article : Google Scholar : PubMed/NCBI
48	Gill AJ, Garza R, Ambegaokar SS, Gelman BB and Kolson DL: Heme oxygenase-1 promoter region (GT)n polymorphism associates with increased neuroimmune activation and risk for encephalitis in HIV infection. J Neuroinflammation. 15:702018. View Article : Google Scholar : PubMed/NCBI
49	Kaplan M, Wong RJ and Stevenson DK: Heme oxygenase-1 promoter polymorphisms: Do they modulate neonatal hyperbilirubinemia? J Perinatol. 37:901–905. 2017. View Article : Google Scholar : PubMed/NCBI
50	Garza R, Gill AJ, Bastien BL, Garcia-Mesa Y, Gruenewald AL, Gelman BB, Tsima B, Gross R, Letendre SL and Kolson DL: Heme oxygenase-1 promoter (GT)n polymorphism associates with HIV neurocognitive impairment. Neurol Neuroimmunol Neuroinflamm. 7:e7102020. View Article : Google Scholar : PubMed/NCBI
51	Chen YH, Lin SJ, Lin MW, Tsai HL, Kuo SS, Chen JW, Charng MJ, Wu TC, Chen LC, Ding YA, et al: 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. View Article : Google Scholar : PubMed/NCBI
52	Yamada N, Yamaya M, Okinaga S, Nakayama K, Sekizawa K, Shibahara S and Sasaki H: Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema. Am J Hum Genet. 66:187–195. 2000. View Article : Google Scholar : PubMed/NCBI
53	Espinoza JA, González PA and Kalergis AM: Modulation of antiviral immunity by heme oxygenase-1. Am J Pathol. 187:487–493. 2017. View Article : Google Scholar : PubMed/NCBI
54	Zhou Y, Wang SN, Li H, Zha W, Peng Q, Li S, Chen Y and Jin L: Quantitative trait analysis of polymorphisms in two bilirubin metabolism enzymes to physiologic bilirubin levels in Chinese newborns. J Pediatr. 165:1154–1160.e1. 2014. View Article : Google Scholar : PubMed/NCBI
55	Wenzel P, Rossmann H, Müller C, Kossmann S, Oelze M, Schulz A, Arnold N, Simsek C, Lagrange J, Klemz R, et al: Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans. Eur Heart J. 36:3437–3446. 2015. View Article : Google Scholar : PubMed/NCBI
56	Pechlaner R, Willeit P, Summerer M, Santer P, Egger G, Kronenberg F, Demetz E, Weiss G, Tsimikas S, Witztum JL, et al: Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease. Arterioscler Thromb Vasc Biol. 35:229–236. 2015. View Article : Google Scholar : PubMed/NCBI
57	Leaf DE, Body SC, Muehlschlegel JD, McMahon GM, Lichtner P, Collard CD, Shernan SK, Fox AA and Waikar SS: Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery. J Am Soc Nephrol. 27:3291–3297. 2016. View Article : Google Scholar : PubMed/NCBI
58	Zhang MM, Zheng YY, Gao Y, Zhang JZ, Liu F, Yang YN, Li XM, Ma YT and Xie X: Heme oxygenase-1 gene promoter polymorphisms are associated with coronary heart disease and restenosis after percutaneous coronary intervention: A meta-analysis. Oncotarget. 7:83437–83450. 2016. View Article : Google Scholar : PubMed/NCBI
59	Ono K, Mannami T and Iwai N: Association of a promoter variant of the haeme oxygenase-1 gene with hypertension in women. J Hypertens. 21:1497–1503. 2003. View Article : Google Scholar : PubMed/NCBI
60	Ellakany WI, Mahmoud MoheyEldin K, Invernizzi P, Mahmoud ElKady A, Eldin Fathy Abou Elkheir H, Abdel Haleem Abo Elwafa R and Ellakany A: Study of the influence of heme oxygenase 1 gene single nucleotide polymorphism (rs2071746) on esophageal varices among patients with cirrhosis. Eur J Gastroenterol Hepatol. 30:888–892. 2018. View Article : Google Scholar : PubMed/NCBI
61	Ono K, Goto Y, Takagi S, Baba S, Tago N, Nonogi H and Iwai N: A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese. Atherosclerosis. 173:313–319. 2004. View Article : Google Scholar : PubMed/NCBI
62	Buis CI, van der Steege G, Visser DS, Nolte IM, Hepkema BG, Nijsten M, Slooff MJ and Porte RJ: Heme oxygenase-1 genotype of the donor is associated with graft survival after liver transplantation. Am J Transplant. 8:377–385. 2008. View Article : Google Scholar : PubMed/NCBI
63	Rich A, Nordheim A and Wang AH: The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 53:791–846. 1984. View Article : Google Scholar : PubMed/NCBI
64	Naylor LH and Clark EM: d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription. Nucleic Acids Res. 18:1595–1601. 1990. View Article : Google Scholar : PubMed/NCBI
65	Kramer M, Sponholz C, Slaba M, Wissuwa B, Claus RA, Menzel U, Huse K, Platzer M and Bauer M: Alternative 5′ untranslated regions are involved in expression regulation of human heme oxygenase-1. PLoS One. 8:e772242013. View Article : Google Scholar : PubMed/NCBI
66	Doberer D, Haschemi A, Andreas M, Zapf TC, Clive B, Jeitler M, Heinzl H, Wagner O, Wolzt M and Bilban M: Haem arginate infusion stimulates haem oxygenase-1 expression in healthy subjects. Br J Pharmacol. 161:1751–1762. 2010. View Article : Google Scholar : PubMed/NCBI
67	Hong CC, Ambrosone CB, Ahn J, Choi JY, McCullough ML, Stevens VL, Rodriguez C, Thun MJ and Calle EE: Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 16:1784–1794. 2007. View Article : Google Scholar : PubMed/NCBI
68	Abraham NG and Kappas A: Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev. 60:79–127. 2008. View Article : Google Scholar : PubMed/NCBI
69	Liang KW, Lee WJ, Lee WL, Wu JP, Lee IT, Wang JS and Sheu WH: Subjects with coronary artery disease and reduced ejection fraction have longer (GT)n repeats in the heme-oxygenase 1 gene promoter. Heart Vessels. 36:615–620. 2021. View Article : Google Scholar : PubMed/NCBI
70	Wu MM, Chiou HY, Chen CL, Hsu LI, Lien LM, Wang CH, Hsieh YC, Wang YH, Hsueh YM, Lee TC, et al: Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: An observation based on arsenic-exposed individuals. Atherosclerosis. 219:704–708. 2011. View Article : Google Scholar : PubMed/NCBI
71	Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med. 340:115–126. 1999. View Article : Google Scholar : PubMed/NCBI
72	Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, Clinton Webb R, Lee ME, Nabel GJ and Nabel EG: Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med. 7:693–698. 2001. View Article : Google Scholar : PubMed/NCBI
73	Ishikawa K, Sugawara D, Wang XP, Suzuki K, Itabe H, Maruyama Y and Lusis AJ: Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor knockout mice. Circ Res. 88:506–512. 2001. View Article : Google Scholar : PubMed/NCBI
74	Tulis DA, Durante W, Peyton KJ, Evans AJ and Schafer AI: Heme oxygenase-1 attenuates vascular remodeling following balloon injury in rat carotid arteries. Atherosclerosis. 155:113–122. 2001. View Article : Google Scholar : PubMed/NCBI
75	Lindenblatt N, Bordel R, Schareck W, Menger MD and Vollmar B: Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo. Arterioscler Thromb Vasc Biol. 24:601–606. 2004. View Article : Google Scholar : PubMed/NCBI
76	Liang KW, Lee WJ, Lee IT, Lee WL, Wang JS, Wu JP and Sheu WHH: Subjects with microvascular angina have longer GT repeats polymorphism in the haem oxygenase-1 gene promoter. Biomarkers. 25:144–148. 2020. View Article : Google Scholar : PubMed/NCBI
77	Raval CM and Lee PJ: Heme oxygenase-1 in lung disease. Curr Drug Targets. 11:1532–1540. 2010. View Article : Google Scholar : PubMed/NCBI
78	Du Y, Zhang H, Xu Y, Ding Y, Chen X, Mei Z, Ding H and Jie Z: Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility. Int J Chron Obstruct Pulmon Dis. 14:2081–2088. 2019. View Article : Google Scholar : PubMed/NCBI
79	Zhou H, Ying X, Liu Y, Ye S, Yan J and Li Y: Genetic polymorphism of heme oxygenase 1 promoter in the occurrence and severity of chronic obstructive pulmonary disease: A meta-analysis. J Cell Mol Med. 21:894–903. 2017. View Article : Google Scholar : PubMed/NCBI
80	Fischer BM, Pavlisko E and Voynow JA: Pathogenic triad in COPD: Oxidative stress, protease-antiprotease imbalance, and inflammation. Int J Chron Obstruct Pulmon Dis. 6:413–421. 2011. View Article : Google Scholar : PubMed/NCBI
81	Zhang JQ, Zhang JQ, Fang LZ, Liu L, Fu WP and Dai LM: Effect of oral N-acetylcysteine on COPD patients with microsatellite polymorphism in the heme oxygenase-1 gene promoter. Drug Des Devel Ther. 9:6379–6387. 2015. View Article : Google Scholar : PubMed/NCBI
82	Zhang ZY, Guan J, Li H, Zhou ZQ and Zhou GW: Heme oxygenase-1 promoter polymorphism protects liver allograft. Indian J Surg. 78:14–19. 2016. View Article : Google Scholar : PubMed/NCBI
83	Soares M, Lin Y, Anrather J, Csizmadia E, Takigami K, Sato K, Grey ST, Colvin RB, Choi AM, Poss KD and Bach FH: Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nat Med. 4:1073–1077. 1998. View Article : Google Scholar : PubMed/NCBI
84	Katori M, Buelow R, Ke B, Ma J, Coito AJ, Iyer S, Southard D, Busuttil RW and Kupiec-Weglinski JW: Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway. Transplantation. 73:287–292. 2002. View Article : Google Scholar : PubMed/NCBI
85	Ozaki KS, Marques GM, Nogueira E, Feitoza RQ, Cenedeze MA, Franco MF, Mazzali M, Soares MP, Pacheco-Silva A and Câmara NO: Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism. Clin Transplant. 22:609–616. 2008. View Article : Google Scholar : PubMed/NCBI
86	Nisula S, Kaukonen KM, Vaara ST, Korhonen AM, Poukkanen M, Karlsson S, Haapio M, Inkinen O, Parviainen I, Suojaranta-Ylinen R, et al: Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: The FINNAKI study. Intensive Care Med. 39:420–428. 2013. View Article : Google Scholar : PubMed/NCBI
87	Vilander LM, Vaara ST, Donner KM, Lakkisto P, Kaunisto MA and Pettilä V; FINNAKI Study Group, : Heme oxygenase-1 repeat polymorphism in septic acute kidney injury. PLoS One. 14:e02172912019. View Article : Google Scholar : PubMed/NCBI
88	Vashist YK, Uzungolu G, Kutup A, Gebauer F, Koenig A, Deutsch L, Zehler O, Busch P, Kalinin V, Izbicki JR and Yekebas EF: Heme oxygenase-1 germ line GTn promoter polymorphism is an independent prognosticator of tumor recurrence and survival in pancreatic cancer. J Surg Oncol. 104:305–311. 2011. View Article : Google Scholar : PubMed/NCBI
89	Okamoto I, Krögler J, Endler G, Kaufmann S, Mustafa S, Exner M, Mannhalter C, Wagner O and Pehamberger H: A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with risk for melanoma. Int J Cancer. 119:1312–1315. 2006. View Article : Google Scholar : PubMed/NCBI
90	Berberat PO, Dambrauskas Z, Gulbinas A, Giese T, Giese N, Künzli B, Autschbach F, Meuer S, Büchler MW and Friess H: Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment. Clin Cancer Res. 11:3790–3798. 2005. View Article : Google Scholar : PubMed/NCBI
91	Sunamura M, Duda DG, Ghattas MH, Lozonschi L, Motoi F, Yamauchi J, Matsuno S, Shibahara S and Abraham NG: Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer. Angiogenesis. 6:15–24. 2003. View Article : Google Scholar : PubMed/NCBI
92	Bukowska-Strakova K, Włodek J, Pitera E, Kozakowska M, Konturek-Cieśla A, Cieśla M, Gońka M, Nowak W, Wieczorek A, Pawińska-Wąsikowska K, et al: Role of HMOX1 promoter genetic variants in chemoresistance and chemotherapy induced neutropenia in children with acute lymphoblastic leukemia. Int J Mol Sci. 22:9882021. View Article : Google Scholar : PubMed/NCBI
93	Tang D, Tang WJ, Shi XL, Li WP, Zhou H, Lu LM and Tao L: Association of the microsatellite (GT)n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma. Acta Otolaryngol. 136:806–811. 2016. View Article : Google Scholar : PubMed/NCBI
94	Zhang L, Song FF, Huang YB, Zheng H, Song FJ and Chen KX: Association between the (GT)n polymorphism of the HO-1 gene promoter region and cancer risk: A meta-analysis. Asian Pac J Cancer Prev. 15:4617–4622. 2014. View Article : Google Scholar : PubMed/NCBI
95	Hu JL, Li ZY, Liu W, Zhang RG, Li GL, Wang T, Ren JH and Wu G: Polymorphism in heme oxygenase-1 (HO-1) promoter and alcohol are related to the risk of esophageal squamous cell carcinoma on Chinese males. Neoplasma. 57:86–92. 2010. View Article : Google Scholar : PubMed/NCBI
96	Lo SS, Lin SC, Wu CW, Chen JH, Yeh WI, Chung MY and Lui WY: Heme oxygenase-1 gene promoter polymorphism is associated with risk of gastric adenocarcinoma and lymphovascular tumor invasion. Ann Surg Oncol. 14:2250–2256. 2007. View Article : Google Scholar : PubMed/NCBI
97	Sawa T, Mounawar M, Tatemichi M, Gilibert I, Katoh T and Ohshima H: Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters. Cancer Lett. 269:78–84. 2008. View Article : Google Scholar : PubMed/NCBI
98	Kikuchi A, Yamaya M, Suzuki S, Yasuda H, Kubo H, Nakayama K, Handa M, Sasaki T, Shibahara S, Sekizawa K and Sasaki H: Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism. Hum Genet. 116:354–360. 2005. View Article : Google Scholar : PubMed/NCBI
99	Jirásková A, Novotný J, Novotný L, Vodicka P, Pardini B, Naccarati A, Schwertner HA, Hubácek JA, Puncochárová L, Šmerhovský Z and Vítek L: Association of serum bilirubin and promoter variations in HMOX1 and UGT1A1 genes with sporadic colorectal cancer. Int J Cancer. 131:1549–1555. 2012. View Article : Google Scholar : PubMed/NCBI
100	Podkalicka P, Mucha O, Józkowicz A, Dulak J and Łoboda A: Heme oxygenase inhibition in cancers: Possible tools and targets. Contemp Oncol (Pozn). 22:32–23. 2018.PubMed/NCBI
101	Kah J, Volz T, Lütgehetmann M, Groth A, Lohse AW, Tiegs G, Sass G and Dandri M: Haem oxygenase-1 polymorphisms can affect HCV replication and treatment responses with different efficacy in humanized mice. Liver Int. 37:1128–1137. 2017. View Article : Google Scholar : PubMed/NCBI
102	Singh D, Wasan H and Reeta KH: Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications. Free Radic Biol Med. 161:263–271. 2020. View Article : Google Scholar : PubMed/NCBI
103	Zhou JF, Luo JY, Zhu WB, Yang CY, Zeng YL and Qiu XL: Association between genetic polymorphism of heme oxygenase 1 promoter and neonatal hyperbilirubinemia: A meta-analysis. J Matern Fetal Neonatal Med. 34:12–23. 2021. View Article : Google Scholar : PubMed/NCBI
104	Wagener FA, Toonen EJ, Wigman L, Fransen J, Creemers MC, Radstake TR, Coenen MJ, Barrera P, van Riel PL and Russel FG: HMOX1 promoter polymorphism modulates the relationship between disease activity and joint damage in rheumatoid arthritis. Arthritis Rheum. 58:3388–3393. 2008. View Article : Google Scholar : PubMed/NCBI
105	Gulla A, Gulbinas A, Dambrauskas Z and Strupas K: Heme oxygenase-1 polymorphism is associated with the development of necrotic acute pancreatitis via vascular cell adhesion molecule-1 and the E-selectin expression regulation pathway. Pancreas. 48:787–791. 2019. View Article : Google Scholar : PubMed/NCBI
106	Lee EY, Lee YH, Kim SH, Chung KS, Kwon O, Kim BS, Nam CM, Park CS, Lee BW, Kang ES, et al: Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes: A case-control study. Medicine (Baltimore). 94:e18252015. View Article : Google Scholar : PubMed/NCBI
107	Holweg CT, Balk AH, Uitterlinden AG, Niesters HG, Maat LP, Weimar W and Baan CC: Functional heme oxygenase-1 promoter polymorphism in relation to heart failure and cardiac transplantation. J Heart Lung Transplant. 24:493–497. 2005. View Article : Google Scholar : PubMed/NCBI
108	Foresti R, Bains SK, Pitchumony TS, de Castro Brás LE, Drago F, Dubois-Randé JL, Bucolo C and Motterlini R: Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells. Pharmacol Res. 76:132–148. 2013. View Article : Google Scholar : PubMed/NCBI
109	Funes SC, Rios M, Fernández-Fierro A, Covián C, Bueno SM, Riedel CA, Mackern-Oberti JP and Kalergis AM: Naturally derived heme-oxygenase 1 inducers and their therapeutic application to immune-mediated diseases. Front Immunol. 11:14672020. View Article : Google Scholar : PubMed/NCBI