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Association of Genetic Variations in NRF2, NQO1, HMOX1, and MT with Severity of Coronary Artery Disease and Related Risk Factors

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Abstract

NRF2 is a transcription factor which, during oxidative stress, activates transcription of its target antioxidant genes. Polymorphisms in NRF2 and its target antioxidant genes: HMOX-1, NQO1, and MT, have been associated with cardiovascular diseases (CVDs) and diabetes in various ethnic groups, however, with variable results. The aim of this study was to investigate the association of NRF2, HMOX-1, NQO1, and MT gene polymorphisms with CVD risk factors in Thais. The study was conducted in two groups: group with high-risk for coronary artery disease (CAD) and health check-up group. Polymorphisms in NRF2 (rs6721961), NQO1 (rs1800566), MT1A (rs11640851), and HMOX-1 (rs2071746) were genotyped. Expressions of NRF2, HMOX-1, and NQO1 were also determined. In high-risk group, NRF2 rs6721961-TT was associated with CAD [OR (95% CI) 5.07 (1.42–18.10)] and severity of coronary atherosclerosis [Gensini score > 32, OR (95% CI) 4.31 (1.67–11.09)]; rs6721961 GT and TT revealed significant association with lower mRNA expression than GG (p = 0.021). NQO1 rs1800566 also revealed association with CAD, only in female. Combined effect of NQO1-rs1800566, HMOX1-rs2071746, and MT1A-rs11640851 was evaluated on the risks of DM and hypertension. With a combination of risk alleles as genetic risk score (GRS), the highest GRS (score 6) increased risk for hypertension, comparing with GRS 0–2 [OR (95% CI) 1.89 (1.02–3.49)]; group with score 5–6 revealed association with risk of DM [OR (95% CI) 1.481 (1.08–2.04)]. In conclusion, NRF2 rs6721961 associated with CAD and severity of coronary atherosclerosis. NQO1 rs1800566 also associated with CAD, only in female. Combined polymorphisms of three NRF2-regulated genes increased risk of DM and hypertension.

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References

  1. Gaziano, T., Reddy, K. S., Paccaud, F., Horton, S., & Chaturvedi, V. (2006). Chapter 33 cardiovascular disease. In D. T. Jamison, J. G. Breman, A. R. Measham, G. Alleyne, M. Claeson, D. B. Evans, et al. (Eds.), Disease control priorities in developing countries (2nd ed., pp. 645–662). Washington: World Bank.

    Google Scholar 

  2. Saha, S., Gerdtham, U. G., & Johansson, P. (2010). Economic evaluation of lifestyle interventions for preventing diabetes and cardiovascular diseases. International Journal of Environmental Research and Public Health,7, 3150–3195.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Al-Mawali, A. (2015). Non-communicable diseases: Shining a light on cardiovascular disease, Oman’s biggest killer. Oman Medical Journal,30, 227–228.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jarachvarawat, C. (2009). Risk factors and prevention of coronary artery disease. Journal of Medicine and Health Sciences,16, 33–41.

    Google Scholar 

  5. WHO. (2014). disease and injury country estimates, 2000-2012. Geneva: World Health Organization.

    Google Scholar 

  6. Kansanen, E., Kuosmanen, S. M., Leinonen, H., & Levonen, A. L. (2013). The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox biology,1, 45–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gu, J., Cheng, Y., Wu, H., Kong, L., Wang, S., Xu, Z., et al. (2017). Metallothionein is downstream of Nrf2 and partially mediates sulforaphane prevention of diabetic cardiomyopathy. Diabetes,66, 529–542.

    Article  CAS  PubMed  Google Scholar 

  8. Howden, R. (2013). Nrf2 and cardiovascular defense. Oxidative Medicine and Cellular Longevity,2013, 104308.

    PubMed  PubMed Central  Google Scholar 

  9. Collins, A. R., Gupte, A. A., Ji, R., Ramirez, M. R., Minze, L. J., Liu, J. Z., et al. (2012). Myeloid deletion of nuclear factor erythroid 2-related factor 2 increases atherosclerosis and liver injury. Arteriosclerosis, Thrombosis, and Vascular Biology,32, 2839–2846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ruotsalainen, A. K., Inkala, M., Partanen, M. E., Lappalainen, J. P., Kansanen, E., Makinen, P. I., et al. (2013). The absence of macrophage Nrf2 promotes early atherogenesis. Cardiovascular Research,98, 107–115.

    Article  CAS  PubMed  Google Scholar 

  11. Shimoyama, Y., Mitsuda, Y., Hamajima, N., & Niwa, T. (2014). Polymorphisms of nrf2, an antioxidative gene, are associated with blood pressure in japanese. Nagoya Journal of Medical Science,76, 113–120.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Hartikainen, J. M., Tengstrom, M., Kosma, V. M., Kinnula, V. L., Mannermaa, A., & Soini, Y. (2012). Genetic polymorphisms and protein expression of NRF2 and Sulfiredoxin predict survival outcomes in breast cancer. Cancer Research,72, 5537–5546.

    Article  CAS  PubMed  Google Scholar 

  13. Suzuki, T., Shibata, T., Takaya, K., Shiraishi, K., Kohno, T., Kunitoh, H., et al. (2013). Regulatory nexus of synthesis and degradation deciphers cellular Nrf2 expression levels. Molecular and Cellular Biology,33, 2402–2412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Atia, A., Alrawaiq, N., & Abdullah, A. (2014). A review of NAD(P)H: Quinone oxidoreductase 1 (NQO1); A multifunctional antioxidant enzyme. Journal of Applied Pharmaceutical Science,4, 118–122.

    Google Scholar 

  15. Yu, H., Liu, H., Wang, L. E., & Wei, Q. (2012). A functional NQO1 609C > T polymorphism and risk of gastrointestinal cancers: A meta-analysis. PLoS ONE,7, e30566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Han, S. J., Kang, E. S., Kim, H. J., Kim, S. H., Chun, S. W., Ahn, C. W., et al. (2009). The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes. Molecular Genetics and Metabolism,97, 85–90.

    Article  CAS  PubMed  Google Scholar 

  17. Traver, R. D., Siegel, D., Beall, H. D., Phillips, R. M., Gibson, N. W., Franklin, W. A., et al. (1997). Characterization of a polymorphism in NAD(P)H: Quinone oxidoreductase (DT-diaphorase). British Journal of Cancer,75, 69–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Siegel, D., McGuinness, S. M., Winski, S. L., & Ross, D. (1999). Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H: Quinone oxidoreductase 1. Pharmacogenetics,9, 113–121.

    Article  CAS  PubMed  Google Scholar 

  19. Traver, R. D., Horikoshi, T., Danenberg, K. D., Stadlbauer, T. H., Danenberg, P. V., Ross, D., et al. (1992). NAD(P)H: Quinone oxidoreductase gene expression in human colon carcinoma cells: Characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Research,52, 797–802.

    CAS  PubMed  Google Scholar 

  20. Gozzelino, R., Jeney, V., & Soares, M. P. (2010). Mechanisms of cell protection by heme oxygenase-1. Annual Review of Pharmacology and Toxicology,50, 323–354.

    Article  CAS  PubMed  Google Scholar 

  21. Morita, T. (2005). Heme oxygenase and atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology,25, 1786–1795.

    Article  CAS  PubMed  Google Scholar 

  22. Zbornikova, P., Kralik, L., Lelkova, P., Kalincik, T., Havrdova, E., & Martasek, P. (2012). Microsatellite polymorphism in haem oxygenase 1 gene promoter in multiple sclerosis. Folia Biologica,58, 69–74.

    CAS  PubMed  Google Scholar 

  23. Lee, E. Y., Lee, Y. H., Kim, S. H., Jung, K. S., Kwon, O., Kim, B. S., et al. (2015). Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes: A case-control study. Medicine,94, e1825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ono, K., Goto, Y., Takagi, S., Baba, S., Tago, N., Nonogi, H., et al. (2004). A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese. Atherosclerosis,173, 315–319.

    Article  CAS  PubMed  Google Scholar 

  25. Thirumoorthy, N., Shyam, S. A., Manisenthil, K. K., Senthil, K. M., Ganesh, G., & Chatterjee, M. (2011). A review of metallothionein isoforms and their role in pathophysiology. World Journal of Surgical Oncology,9, 54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sabolic, I., Breljak, D., Skarica, M., & Herak-Kramberger, C. M. (2010). Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. BioMetals,23, 897–926.

    Article  CAS  PubMed  Google Scholar 

  27. Yang, L., Li, H., Yu, T., Zhao, H., Cherian, M. G., Cai, L., et al. (2008). Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications. American journal of physiology. Endocrinology and Metabolism,294, E987–E992.

    CAS  PubMed  Google Scholar 

  28. Gensini, G. G. (1983). A more meaningful scoring system for determining the severity of coronary heart disease. American Journal of Cardiology,51, 606.

    Article  CAS  Google Scholar 

  29. Yongsakulchai, P., Settasatian, C., Settasatian, N., Komanasin, N., Kukongwiriyapan, U., Cote, M. L., et al. (2016). Association of combined genetic variations in PPARgamma, PGC-1alpha, and LXRalpha with coronary artery disease and severity in Thai population. Atherosclerosis,248, 140–148.

    Article  CAS  PubMed  Google Scholar 

  30. American Diabetes Association. (2013). Standards of medical care in diabetes—2013. Diabetes Care,36(Suppl 1), S11–S66.

    Article  CAS  Google Scholar 

  31. Weber, M. A., Schiffrin, E. L., White, W. B., Mann, S., Lindholm, L. H., Kenerson, J. G., et al. (2014). Clinical practice guidelines for the management of hypertension in the community: A statement by the American Society of Hypertension and the International Society of Hypertension. Journal of Clinical Hypertension (Greenwich),16, 14–26.

    Article  Google Scholar 

  32. WHO. (2000). The Asia-Pacific perspective: Redefining obesity and its treatment (pp. 1–55). Australia Western Pacific Region: World Health Organization.

    Google Scholar 

  33. NCEP-ATP III. (2002). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation, 106, 3143–3421.

    Article  Google Scholar 

  34. Shimoyama, Y., Mitsuda, Y., Tsuruta, Y., Hamajima, N., & Niwa, T. (2014). Polymorphism of Nrf2, an antioxidative gene, is associated with blood pressure and cardiovascular mortality in hemodialysis patients. International Journal of Medical Sciences,11, 726–731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., & Madden, T. L. (2012). Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics,13, 134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Giegerich, R., Meyer, F., & Schleiermacher, C. (1996). GeneFisher—Software support for the detection of postulated genes. Proceedings of the 3rd International Conference on Intelligent Systems for Molecular Biology,4, 68–77.

    CAS  Google Scholar 

  37. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods,25, 402–408.

    Article  CAS  PubMed  Google Scholar 

  38. Lastra, G., Syed, S., Kurukulasuriya, L. R., Manrique, C., & Sowers, J. R. (2014). Type 2 diabetes mellitus and hypertension: An update. Endocrinology and Metabolism Clinics of North America,43, 103–122.

    Article  PubMed  Google Scholar 

  39. Ohishi, M. (2018). Hypertension with diabetes mellitus: Physiology and pathology. Hypertension Research,41, 389–393.

    Article  PubMed  Google Scholar 

  40. Khan, K. A., Govindarajan, G., Whaley-Connell, A., & Sowers, J. R. (2006). Diabetic hypertension. Heart Failure Clinics,2, 25–36.

    Article  PubMed  Google Scholar 

  41. Kunnas, T., Maatta, K., & Nikkari, S. T. (2016). Genetic polymorphisms of transcription factor NRF2 and of its host gene sulfiredoxin (SRXN1) are associated with cerebrovascular disease in a Finnish Cohort, the TAMRISK Study. International Journal of Medical Sciences,13, 325–329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Marzec, J. M., Christie, J. D., Reddy, S. P., Jedlicka, A. E., Vuong, H., Lanken, P. N., et al. (2007). Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB Journal,21, 2237–2246.

    Article  CAS  PubMed  Google Scholar 

  43. Cho, H. Y., Marzec, J., & Kleeberger, S. R. (2015). Functional polymorphisms in Nrf2: Implications for human disease. Free Radical Biology & Medicine,88, 362–372.

    Article  CAS  Google Scholar 

  44. Ross, D., Kepa, J. K., Winski, S. L., Beall, H. D., Anwar, A., & Siegel, D. (2000). NAD(P)H: Quinone oxidoreductase 1 (NQO1): Chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chemico-Biological Interactions,129, 77–97.

    Article  CAS  PubMed  Google Scholar 

  45. Martin, N. J., Collier, A. C., Bowen, L. D., Pritsos, K. L., Goodrich, G. G., Arger, K., et al. (2009). Polymorphisms in the NQO1, GSTT and GSTM genes are associated with coronary heart disease and biomarkers of oxidative stress. Mutation Research,674, 93–100.

    Article  CAS  PubMed  Google Scholar 

  46. Boroumand, M., Pourgholi, L., Goodarzynejad, H., Ziaee, S., Hajhosseini-Talasaz, A., Sotoudeh-Anvari, M., et al. (2017). NQO1 C609T polymorphism is associated with coronary artery disease in a gender-dependent manner. Cardiovascular Toxicology,17, 35–41.

    Article  CAS  PubMed  Google Scholar 

  47. Cheng, Y., Li, J., Martinka, M., & Li, G. (2010). The expression of NAD(P)H: Quinone oxidoreductase 1 is increased along with NF-kappaB p105/p50 in human cutaneous melanomas. Oncology Reports,23, 973–979.

    CAS  PubMed  Google Scholar 

  48. Augustine, L. M., Fisher, C. D., Lickteig, A. J., Aleksunes, L. M., Slitt, A. L., & Cherrington, N. J. (2008). Gender divergent expression of Nqo1 in Sprague Dawley and August Copenhagen x Irish rats. Journal of Biochemical and Molecular Toxicology,22, 93–100.

    Article  CAS  PubMed  Google Scholar 

  49. Yin, J., Wang, L., Wang, X., Zheng, L., Shi, Y., Shao, A., et al. (2014). NQO1 rs1800566 C > T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population. Scandinavian Journal of Gastroenterology,49, 317–322.

    Article  CAS  PubMed  Google Scholar 

  50. Ding, R., Lin, S., & Chen, D. (2012). Association of NQO1 rs1800566 polymorphism and the risk of colorectal cancer: A meta-analysis. International Journal of Colorectal Disease,27, 885–892.

    Article  PubMed  Google Scholar 

  51. Wang, G., Zhang, L., & Li, Q. (2006). Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population. Biochemical and Biophysical Research Communications,341, 310–313.

    Article  CAS  PubMed  Google Scholar 

  52. Joseph, P., & Jaiswal, A. K. (1994). NAD(P)H:quinone oxidoreductase1 (DT diaphorase) specifically prevents the formation of benzo[a]pyrene quinone-DNA adducts generated by cytochrome P4501A1 and P450 reductase. Proceedings of the National Academy of Sciences of the United States,91, 8413–8417.

    Article  CAS  Google Scholar 

  53. Cadenas, E. (1995). Antioxidant and prooxidant functions of DT-diaphorase in quinone metabolism. Biochemical Pharmacology,49, 127–140.

    Article  CAS  PubMed  Google Scholar 

  54. Ross, D., & Siegel, D. (2017). Functions of NQO1 in cellular protection and CoQ10 metabolism and its potential role as a redox sensitive molecular switch. Frontiers in Physiology,8, 595.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Ono, K., Mannami, T., & Iwai, N. (2003). Association of a promoter variant of the haeme oxygenase-1 gene with hypertension in women. Journal of Hypertension,21, 1497–1503.

    Article  CAS  PubMed  Google Scholar 

  56. Lin, R., Fu, W., Zhou, W., Wang, Y., Wang, X., Huang, W., et al. (2011). Association of heme oxygenase-1 gene polymorphisms with essential hypertension and blood pressure in the Chinese Han population. Genetic Testing and Molecular Biomarkers,15, 23–28.

    Article  CAS  PubMed  Google Scholar 

  57. Solari, V., Piotrowska, A. P., & Puri, P. (2003). Expression of heme oxygenase-1 and endothelial nitric oxide synthase in the lung of newborns with congenital diaphragmatic hernia and persistent pulmonary hypertension. Journal of Pediatric Surgery,38, 808–813.

    Article  PubMed  Google Scholar 

  58. Stanford, S. J., Walters, M. J., Hislop, A. A., Haworth, S. G., Evans, T. W., Mann, B. E., et al. (2003). Heme oxygenase is expressed in human pulmonary artery smooth muscle where carbon monoxide has an anti-proliferative role. European Journal of Pharmacology,473, 135–141.

    Article  CAS  PubMed  Google Scholar 

  59. Stec, D. E., Drummond, H. A., & Vera, T. (2008). Role of carbon monoxide in blood pressure regulation. Hypertension,51, 597–604.

    Article  CAS  PubMed  Google Scholar 

  60. Schulz, E., Jansen, T., Wenzel, P., Daiber, A., & Munzel, T. (2008). Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxidants & Redox Signaling,10, 1115–1126.

    Article  CAS  Google Scholar 

  61. Ceylan-Isik, A. F., Guo, K. K., Carlson, E. C., Privratsky, J. R., Liao, S. J., Cai, L., et al. (2009). Metallothionein abrogates GTP cyclohydrolase I inhibition-induced cardiac contractile and morphological defects: Role of mitochondrial biogenesis. Hypertension,53, 1023–1031.

    Article  CAS  PubMed  Google Scholar 

  62. Choi, S., Liu, X., & Pan, Z. (2018). Zinc deficiency and cellular oxidative stress: Prognostic implications in cardiovascular diseases. Acta Pharmacologica Sinica,39, 1120–1132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Giacconi, R., Bonfigli, A. R., Testa, R., Sirolla, C., Cipriano, C., Marra, M., et al. (2008). +647 A/C and +1245 MT1A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications. Molecular Genetics and Metabolism,94, 98–104.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The financial support for this study was from National Research Council of Thailand (NRCT), Ingkarat Sarutipaiboon was supported by a Research Fund for Supporting Lecturer to Admit High Potential Student to Study and Research on His Expert Program Year 2012 (551H208); and Cardiovascular Research Group (CVRG), Khon Kaen University. The Faculty of Associated Medical Sciences, Khon Kaen University had provided all necessary facilities throughout the study.

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Authors and Affiliations

  1. Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, 40002, Thailand

    Ingkarat Sarutipaiboon

  2. School of Medical Technology, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

    Nongnuch Settasatian & Nantarat Komanasin

  3. Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Upa Kukongwiriyapan

  4. Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Kittisak Sawanyawisuth & Vichai Senthong

  5. Queen Sirikit Heart Center of the Northeast Hospital, Khon Kaen University, Khon Kaen, 40002, Thailand

    Phongsak Intharaphet & Vichai Senthong

  6. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Chatri Settasatian

  7. Cardiovascular Research Group, Khon Kaen University, Khon Kaen, 40002, Thailand

    Ingkarat Sarutipaiboon, Nongnuch Settasatian, Nantarat Komanasin, Upa Kukongwiriyapan, Phongsak Intharaphet, Vichai Senthong & Chatri Settasatian

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Ethical Approval

This study involved human data and protocol was approved by the Khon Kaen University Ethics Committee for Human Research (HE 510414 for the high-risk group and HE 601094 for the health check-up group) based on the Declaration of Helsinki and the ICH Good Clinical Practice Guidelines.

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The high-risk group had voluntarily joined a study and provide written consent forms as well as demographic data and the basic information according to the questionnaire. All consent forms have been reviewed by the Khon Kaen University Ethics Committee for Human Research. For the health check-up group, because the data were obtained from retrospective medical records accompanied with collected left-over samples, formal consent was not required.

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Sarutipaiboon, I., Settasatian, N., Komanasin, N. et al. Association of Genetic Variations in NRF2, NQO1, HMOX1, and MT with Severity of Coronary Artery Disease and Related Risk Factors. Cardiovasc Toxicol 20, 176–189 (2020). https://doi.org/10.1007/s12012-019-09544-7

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