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Gene polymorphisms and thyroid function in patients with heart failure

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Abstract

We evaluated nuclear factor kappa B {NFkB, rs28362491 [−94ins/delATTG (W/D)]} and angiotensin converting enzyme {ACE; rs1799752 [Ins(I)/Del(D)]} gene polymorphisms and their correlation with thyroid function in patients with heart failure (HF). Peak oxygen uptake (VO2) was evaluated (by Weber classification) during a symptom-limited cardiopulmonary exercise test in 194 patients. Thyroid-stimulating hormone, triiodothyronine (T3), thyroxine (T4), and free (F) T3 and FT4 were also measured. According to their cardiovascular (CV) capacity, patients were subdivided into four groups: group A included patients with peak VO2 >20 ml/kg/min, group B 16–20 ml/kg/min, group C 10–16 ml/kg/min, and group D 6–10 ml/kg/min. Patients were also genotyped for NFkB and ACE genetic variants. T3 was increased and FT3 was decreased for every raise in Weber’s classification (p = 0.007 and p = 0.012, respectively). Del carriers had elevated FT3 levels compared with Ins carriers (p = 0.021). Patients with II genotype had elevated T4 levels compared with ID genotype (p = 0.044). Both T4 and FT4 were decreased in D allele carriers (p = 0.007 and p = 0.045, respectively). Thyroid hormones correlated with CV capacity. Associations between the NFkB and ACE gene polymorphisms and thyroid hormones levels were also observed. Further larger studies are required to clarify genes contribution in HF.

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References

  1. G.V. Ramani, P.A. Uber, M.R. Mehra, Chronic heart failure: contemporary diagnosis and management. Mayo Clin. Proc. 85, 180–195 (2010)

    Article  PubMed  Google Scholar 

  2. A. Gluba, A. Bielecka, D.P. Mikhailidis, N.D. Wong, S.S. Franklin, J. Rysz, M. Banach, An update on biomarkers of heart failure in hypertensive patients. J. Hypertens. 30, 1681–1689 (2012)

    Article  CAS  PubMed  Google Scholar 

  3. G. Karayannis, G. Giamouzis, N. Tziolas, P. Georgoulias, J. Skoularigis, D.P. Mikhailidis, F. Triposkiadis, Association between epicardial fat thickness and weight homeostasis hormones in patients with noncachectic heart failure. Angiology. 2012 May 30 [Epub ahead of print]

  4. S. Danzi, I. Klein, Thyroid hormone and the cardiovascular system. Med. Clin. N. Am. 96, 257–268 (2012)

    Article  CAS  PubMed  Google Scholar 

  5. L.Q. Gu, L. Zhao, W. Zhu, F.Y. Li, M.J. Zhang, Y. Liu, J.M. Liu, G. Ning, Y.J. Zhao, Relationships between serum levels of thyroid hormones and serum concentrations of asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) in patients with Graves’ disease. Endocrine 38, 266–271 (2011)

    Article  Google Scholar 

  6. A. Kırış, C. Erem, G. Kırış, M. Koçak, O. Gedikli, I. Nuhoğlu, M. Kutlu, T. Kaplan, M. Gökçe, S. Celik, Intra-left ventricular systolic asynchrony in patients with overt hyperthyroidism. Endocrine 39, 283–288 (2010)

    Google Scholar 

  7. N. Rodondi, A.B. Newman, E. Vittinghoff, N. de Rekeneire, S. Satterfield, T.B. Harris, D.C. Bauer, Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch. Intern. Med. 165, 2460–2466 (2005)

    Article  PubMed  Google Scholar 

  8. E. Kiss, G. Jakab, E.G. Kranias, I. Edes, Thyroid hormone-induced alterations in phospholamban protein expression: regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation. Circ. Res. 75, 245–251 (1994)

    Article  CAS  PubMed  Google Scholar 

  9. I. Klein, K. Ojamaa, Thyroid hormone and the cardiovascular system. N. Engl. J. Med. 344, 501–509 (2001)

    Article  CAS  PubMed  Google Scholar 

  10. P.W. Ladenson, S.I. Sherman, R.L. Baughman, P.E. Ray, A.M. Feldman, Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism. Proc. Natl. Acad. Sci. 89, 5251–5255 (1992)

    Article  CAS  PubMed  Google Scholar 

  11. K. Ojamaa, A. Sabet, A. Kenessey, R. Shenoy, I. Klein, Regulation of rat cardiac Kv1.5 gene expression by thyroid hormone is rapid and chamber specific. Endocrinology 140, 3170–3176 (1999)

    CAS  PubMed  Google Scholar 

  12. B.D. Hoit, S.F. Khoury, Y. Shao, M. Gabel, S.B. Liggett, R.A. Walsh, Effects of thyroid hormone on cardiac beta-adrenergic responsiveness in conscious baboons. Circulation 96, 592–598 (1997)

    Article  CAS  PubMed  Google Scholar 

  13. H.L. Pahl, Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18, 6853–6866 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. G. Valen, Z.Q. Yan, G.K. Hansson, Nuclear factor kappa-B and the heart. J. Am. Coll. Cardiol. 38, 307–314 (2001)

    Article  CAS  PubMed  Google Scholar 

  15. B. Agerholm-Larsen, B.G. Nordestgaard, R. Steffensen, T.I. Sørensen, G. Jensen, A. Tybjaerg-Hansen, ACE gene polymorphism: ischemic heart disease and longevity in 10,150 individuals. A case-referent and retrospective cohort study based on the Copenhagen City Heart Study. Circulation 95, 2358–2367 (1997)

    Article  CAS  PubMed  Google Scholar 

  16. P.A. McKee, W.P. Castelli, P.M. McNamara, W.B. Kannel, The natural history of congestive heart failure: the Framingham study. N. Engl. J. Med. 285, 1441–1446 (1971)

    Article  CAS  PubMed  Google Scholar 

  17. S.A. Hunt, ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112, e154–e235 (2005)

    Article  PubMed  Google Scholar 

  18. S.A. Hunt, Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration with the International Society for Heart and Lung Transplantation. J. Am. Coll. Cardiol. 54, 2464 (2009)

    Google Scholar 

  19. M. Guazzi, J. Myers, J. Abella, M.A. Peberdy, D. Bensimhon, P. Chase, R. Arena, The added prognostic value of ventilatory efficiency to the Weber classification system in patients with heart failure. Int. J. Cardiol. 129, 86–92 (2008)

    Article  PubMed  Google Scholar 

  20. C. Zugck, C. Krüger, R. Kell, S. Körber, D. Schellberg, W. Kübler, M. Haass, Risk stratification in middle-aged patients with congestive heart failure: prospective comparison of the Heart Failure Survival Score (HFSS) and a simplified two-variable model. Eur. J. Heart Fail. 3, 577–585 (2001)

    Article  CAS  PubMed  Google Scholar 

  21. W.R. Thompson, ACSM’s guidelines for exercise testing and prescription, 8th edn. (Lippincott Williams & Wilkins, Philadelphia, 2010)

    Google Scholar 

  22. American Thoracic Society/American College of Chest Physicians, Statement on cardiopulmonary exercise testing. Am. J. Respir. Crit. Care Med. 167, 211–217 (2003)

    Google Scholar 

  23. R. Arena, J. Myers, M.A. Williams, M. Gulati, P. Kligfield, G.J. Balady, E. Collins, G. Fletcher, Assessment of functional capacity in clinical and research settings. A Scientific Statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation 116, 329–343 (2007)

    Article  PubMed  Google Scholar 

  24. M.J. Obregon, A. Pascual, G.M. de Escobar, F. Escobar del Rey, Pituitary and plasma thyrotropin, thyroxine, and triiodothyronine after hyperthyroidism. Endocrinology 104, 1467–1473 (1979)

    Article  CAS  PubMed  Google Scholar 

  25. J. Glas, H.P. Török, L. Tonenchi, B. Müller-Myhsok, T. Mussack, M. Wetzke, W. Klein, J.T. Epplen, T. Griga, U. Schiemann, P. Lohse, J. Seiderer, F. Schnitzler, S. Brand, T. Ochsenkühn, M. Folwaczny, C. Folwaczny, Role of the NFKB1 −94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes. Inflamm. Bowel Dis. 12, 606–611 (2006)

    Article  PubMed  Google Scholar 

  26. B. Rigat, C. Hubert, P. Corvol, F. Soubrier, PCR detectrion of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 20, 1433 (1992)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. T. Feldman, K.M. Borow, D.H. Sarne, A. Neumann, R.M. Lang, Myocardial mechanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state. J. Am. Coll. Cardiol. 7, 967–974 (1986)

    Article  CAS  PubMed  Google Scholar 

  28. I. Mourouzis, P. Mantzouratou, G. Galanopoulos, E. Kostakou, N. Roukounakis, A.D. Kokkinos, D.V. Cokkinos, C. Pantos, Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings. Mol. Cell. Biochem. 363, 235–243 (2012)

    Article  CAS  PubMed  Google Scholar 

  29. E. Galli, A. Pingitore, G. Iervasi, The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence. Heart Fail. Rev. 15, 155–169 (2010)

    Article  CAS  PubMed  Google Scholar 

  30. I. Klein, The cardiovascular system in thyrotoxicosis, in Werner & Ingbar’s the thyroid: a fundamental and clinical text, 8th edn., ed. by L.E. Braverman, R.D. Utiger (Lippincott Williams &Wilkins, Philadelphia, 2000) pp. 596–604

  31. A. Pingitore, G. Iervasi, Triiodothyronine (T3) effects on cardiovascular system in patients with heart failure. Recent Pat. Cardiovasc. Drug Discov. 3, 19–27 (2008)

    Article  CAS  PubMed  Google Scholar 

  32. I. Lymvaios, I. Mourouzis, D.V. Cokkinos, M.A. Dimopoulos, S.T. Toumanidis, C. Pantos, Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association? Eur. J. Endocrinol. 165, 107–114 (2011)

    Article  CAS  PubMed  Google Scholar 

  33. C. Pantos, A. Dritsas, I. Mourouzis, A. Dimopoulos, G. Karatasakis, G. Athanassopoulos, S. Mavrogeni, A. Manginas, D.V. Cokkinos, Thyroid hormone is a critical determinant of myocardial performance in patients with heart failure: potential therapeutic implications. Eur. J. Endocrinol. 157, 515–520 (2007)

    Article  CAS  PubMed  Google Scholar 

  34. D.G. Santos, M.F. Resende, J.G. Mill, A.J. Mansur, J.E. Krieger, A.C. Pereira, Nuclear Factor (NF) êB polymorphism is associated with heart function in patients with heart failure. BMC Med. Genet. 11, 89 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  35. G. Loncar, B. Bozic, V. Cvorovic, Z. Radojicic, S. Dimkovic, N. Markovic, N. Prodanovic, T. Lepic, B. Putnikovic, V. Popovic-Brkic, Relationship between RANKL and neuroendocrine activation in elderly males with heart failure. Endocrine 37, 148–156 (2010)

    Article  CAS  PubMed  Google Scholar 

  36. A.S. Karban, T. Okazaki, C.I. Panhuysen, T. Gallegos, J.J. Potter, J.E. Bailey-Wilson, M.S. Silverberg, R.H. Duerr, J.H. Cho, P.K. Gregersen, Y. Wu, J.P. Achkar, T. Dassopoulos, E. Mezey, T.M. Bayless, F.J. Nouvet, S.R. Brant, Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis. Hum. Mol. Genet. 13, 35–45 (2004)

    Article  CAS  PubMed  Google Scholar 

  37. B. Zhou, L. Rao, Y. Peng, Y. Wang, Y. Li, L. Gao, Y. Chen, H. Xue, Y. Song, M. Liao, L. Zhang, Functional polymorphism of the NFKB1 gene promoter is related to the risk of dilated cardiomyopathy. BMC Med. Genet. 10, 47 (2009)

    Article  PubMed Central  PubMed  Google Scholar 

  38. B.R. Palmer, A.P. Pilbrow, T.G. Yandle, C.M. Frampton, A.M. Richards, M.G. Nicholls, V.A. Cameron, Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction. J. Am. Coll. Cardiol. 41, 729–736 (2003)

    Article  CAS  PubMed  Google Scholar 

  39. M.S. Ulgen, O. Ozturk, S. Alan, M. Kayrak, Y. Turan, S. Tekes, N. Toprak, The relationship between angiotensin-converting enzyme (insertion/deletion) gene polymorphism and left ventricular remodeling in acute myocardial infarction. Coron. Artery Dis. 18, 153–157 (2007)

    Article  PubMed  Google Scholar 

  40. J. Nagashima, H. Musha, T. So, T. Kunishima, S. Nobuoka, M. Murayama, Effect of angiotensin-converting enzyme gene polymorphism on left ventricular remodeling after anteroseptal infarction. Clin. Cardiol. 22, 587–590 (1999)

    Article  CAS  PubMed  Google Scholar 

  41. R.Y.L. Zee, S.D. Solomon, U.A. Ajani, M.A. Pfeffer, K. Lindpaintner, A prospective evaluation of the angiotensin-converting enzyme D/I polymorphism and left ventricular remodeling in the ‘Healing and Early Afterload Reducing Therapy’ Study. Clin. Genet. 61, 21–25 (2002)

    Article  CAS  PubMed  Google Scholar 

  42. Y. Bai, L. Wang, S. Hu, Y. Wei, Association of angiotensin-converting enzyme I/D polymorphism with heart failure: a meta-analysis. Mol. Cell. Biochem. 361, 297–304 (2012)

    Article  CAS  PubMed  Google Scholar 

  43. G. Atzmon, N. Barzilai, J.G. Hollowell, M.I. Surks, I. Gabriely, Extreme longevity is associated with increased serum thyrotropin. J. Clin. Endocrinol. Metab. 94, 1251–1254 (2009)

    Article  CAS  PubMed  Google Scholar 

  44. S.J. Hauck, W.S. Hunter, N. Danilovich, J.J. Kopchick, A. Bartke, Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse. Exp. Biol. Med. (Maywood) 226, 552–558 (2001)

    CAS  Google Scholar 

  45. P.S. Hansen, T.H. Brix, I. Iachine, T.I. Sørensen, K.O. Kyvik, L. Hegedüs, Genetic and environmental interrelations between measurements of thyroid function in a healthy Danish twin population. Am. J. Physiol. Endocrinol. Metab. 292, E765–E770 (2007)

    Article  CAS  PubMed  Google Scholar 

  46. P.B. Samollow, G. Perez, C.M. Kammerer, D. Finegold, P.W. Zwartjes, L.M. Havill, A.G. Comuzzie, M.C. Mahaney, H.H. Göring, J. Blangero, T.P. Foley, M.M. Barmada, Genetic and environmental influences on thyroid hormone variation in Mexican Americans. J. Clin. Endocrinol. Metab. 89, 3276–3284 (2004)

    Google Scholar 

  47. L. Goumidi, K. Gauthier, V. Legry, T.H. Mayi, A. Houzet, D. Cottel, M. Montaye, C. Proust, F. Kee, J. Ferrières, D. Arveiler, P. Ducimetière, B. Staels, J. Dallongeville, G. Chinetti, F. Flamant, P. Amouyel, A. Meirhaeghe, Association between a thyroid hormone receptor-α gene polymorphism and blood pressure but not with coronary heart disease risk. Am. J. Hypertens. 24, 1027–1034 (2011)

    Article  CAS  PubMed  Google Scholar 

  48. P. Moruzzi, E. Doria, P.G. Agostoni, V. Capacchione, P. Sganzerla, Usefulness of L-thyroxine to improve cardiac and exercise performance in idiopathic dilated cardiomyopathy. Am. J. Cardiol. 73, 374–378 (1994)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was conducted independently; no company or institution supported the authors financially or by providing a professional writer. Some of the authors have given talks, attended conferences, and participated in trials sponsored by various pharmaceutical companies.

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Authors and Affiliations

  1. Cardiology Department, Onassis Cardiac Surgery Center Athens, 356 Sygrou Ave, 176 74, Athens, Greece

    Ioannis Vasiliadis, Genovefa Kolovou, Vana Kolovou, Maria Boutsikou, Evaggelia Papadopoulou, Sophie Mavrogeni, Konstantina Sorontila & Dennis V. Cokkinos

  2. Molecular Immunology Laboratory, Onassis Cardiac Surgery Center, Athens, Greece

    Vana Kolovou

  3. Thriassio Hospital, Elefsina, Greece

    Vasiliki Giannakopoulou

  4. Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece

    Niki Katsiki

  5. Department of Pharmacology, University of Athens, Athens, Greece

    Costas Pantos

  6. Cardiovascular Department, Biomedical Research Foundation Academy of Athens, Athens, Greece

    Dennis V. Cokkinos

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  1. Ioannis Vasiliadis
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  2. Genovefa Kolovou
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Correspondence to Genovefa Kolovou.

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Vasiliadis, I., Kolovou, G., Kolovou, V. et al. Gene polymorphisms and thyroid function in patients with heart failure. Endocrine 45, 46–54 (2014). https://doi.org/10.1007/s12020-013-9926-x

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