Ukr.Biochem.J. 2026; Volume 98, Issue 3, May-Jun, pp. 93-100

doi: https://doi.org/10.15407/ubj98.03.093

Association of BNP gene SNP rs198389 with NT-proBNP levels in hypothyroid patients prior to treatment

09.06.2026   Uncategorized
Alaa Salman

Ishtar Medical Technical Institute, Iraq;
e-mail: alaas3223@gmail.com

Received: 22 March 2026; Revised: 21 April 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026

Background. Cardiovascular system is particularly responsive to fluctuations in thyroid hormone levels and hypothyroid patients are at an increased risk of worse cardiovascular outcomes. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a recognised biomarker for heart failure. Several studies indicate that thyroid disorders may influence blood NT-proBNP level, nevertheless, a consensus has not been established. Objective. To investigate the impact of the single nucleotide polymorphism rs198389 in NT-proBNP gene on the NT-proBNP serum level in patients with untreated primary hypothyroidism. Methods. The study included 100 newly diagnosed hypothyroid patients and 100 healthy controls, with NT-proBNP level measu­red with enzyme-linked fluorescent assay and genetic analysis conducted via PCR. Results. Our findings indicated significantly elevated NT-proBNP level across all genotypes (CC, CT, TT) in hypothyroid patients compared to controls. This elevation correlated strongly with thyroid-stimulating hormone level. Conclusions. The study demonstrated that NT-proBNP can discriminate between hypothyroid patients and healthy controls, but further studies are needed to establish its role in cardiovascular risk prediction.

Keywords: , , , ,

References:

  1. McDermott MT, Ridgway EC. Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Metab. 2001;86(10):4585-4590. PubMed, CrossRef
  2. Godbole NP, Koester M, Marcus EN. Hypothyroidism in Adult Women: The Utility of Targeted vs Universal Thyroid Screening. Int J Womens Health. 2023;15:1515-1522. PubMed, PubMedCentral, CrossRef
  3. Gluvic ZM, Zafirovic SS, Obradovic MM, Sudar-Milovanovic EM, Rizzo M, Isenovic ER. Hypothyroidism and Risk of Cardiovascular Disease. Curr Pharm Des. 2022;28(25):2065-2072. PubMed, CrossRef
  4. Yamakawa H, Kato TS, Noh JY, Yuasa S, Kawamura A, Fukuda K, Aizawa Y. Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside. Front Physiol. 2021;12:606931. PubMed, PubMedCentral, CrossRef
  5. Zúñiga D, Balasubramanian S, Mehmood KT, Al-Baldawi S, Zúñiga Salazar G. Hypothyroidism and Cardiovascular Disease: A Review. Cureus. 2024;16(1):e52512. PubMed, PubMedCentral, CrossRef
  6. Berezin AE, Berezin AA. Biomarkers in Heart Failure: From Research to Clinical Practice. Ann Lab Med. 2023;43(3):225-236. PubMed, PubMedCentral, CrossRef
  7. Willinger L, Brudy L, Häcker AL, Meyer M, Hager A, Oberhoffer-Fritz R, Ewert P, Müller J. High-sensitive troponin T and N-terminal pro-B-type natriuretic peptide independently predict survival and cardiac-related events in adults with congenital heart disease. Eur J Cardiovasc Nurs. 2024;23(1):55-61. PubMed, CrossRef
  8. Iacoviello M, Parisi G, Gioia MI, Grande D, Rizzo C, Guida P, Lisi F, Giagulli VA, Licchelli B, Di Serio F, Guastamacchia E, Triggiani V. Thyroid Disorders and Prognosis in Chronic Heart Failure: A Long-Term Follow-Up Study. Endocr Metab Immune Disord Drug Targets. 2020;20(3):437-445. PubMed, CrossRef
  9. Alcidi G, Goffredo G, Correale M, Brunetti ND, Iacoviello M. Brain Natriuretic Peptide Biomarkers in Current Clinical and Therapeutic Scenarios of Heart Failure. J Clin Med. 2022;11(11):3192. PubMed, PubMedCentral, CrossRef
  10. Cao Z, Jia Y, Zhu B. BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine. Int J Mol Sci. 2019;20(8):1820. PubMed, PubMedCentral, CrossRef
  11. Cozma LCD, Szalontay AS, Cozma S, Dascalu CG, Cojocaru DC, Mitu F, Bitere O, Ghiciuc CM. Uric acid and NT-proBNP as biomarkers of cardiovascular dysfunction in hyperthyroidism and hypothyroidism. Rev Chim. 2017;68(12):2959-2962. CrossRef
  12. Samuel NA, Cuthbert JJ, Brown OI, Kazmi S, Cleland JGF, Rigby AS, Clark AL. Relation Between Thyroid Function and Mortality in Patients With Chronic Heart Failure. Am J Cardiol. 2021;139:57-63. PubMed, CrossRef
  13. Arikan S, Tuzcu A, Gokalp D, Bahceci M, Danis R. Hyperthyroidism may affect serum N-terminal pro-B-type natriuretic peptide levels independently of cardiac dysfunction. Clin Endocrinol (Oxf). 2007;67(2):202-207. PubMed, CrossRef
  14. Pakuła D, Marek B, Kajdaniuk D, Krysiak R, Kos-Kudła B, Pakuła P, Gatnar A, Borgiel-Marek H, Nowak M, Siemińska L, Głogowska-Szeląg J, Ostrowska Z. Plasma levels of NT-pro-brain natriuretic peptide in patients with overt and subclinical hyperthyroidism and hypothyroidism. Endokrynol Pol. 2011;62(6):523-528. PubMed
  15. Xhaard C, Rouget R, Vodovar N, Le Floch E, Dandine-Roulland C, Wagner S, Bacq-Daian D, Thuillier Q, Boivin JM, Branlant C, Deleuze JF, Behm-Ansmant I, Zannad F, Rossignol P, Girerd N. Impact of natriuretic peptide polymorphisms on diastolic and metabolic function in a populational cohort: insights from the STANISLAS cohort. ESC Heart Fail. 2022;9(1):729-739. PubMed, PubMedCentral, CrossRef
  16. Al-Ibrahimi AS, Al-Gazally ME, Alshok MM. Effect of natriuretic peptides (BNP) gene T-381C polymorphism on the levels of BNP and NT-proBNP in patients with cardiovascular disease. Int J PharmTech Res. 2016;9(12):223-229.
  17. Ahmed Shekha G, Asaaf Maulood K, Sabir Shekha M. Relationship between lipid profile and B‑type natriuretic peptide T‑381C (rs198389) gene polymorphism in patients with stable coronary artery disease. Cell Mol Biol. 2023;69(13):180-188. PubMed, CrossRef
  18. Costello-Boerrigter LC, Boerrigter G, Ameenuddin S, Mahoney DW, Slusser JP, Heublein DM, Redfield MM, Rodeheffer RJ, Olson TM, Burnett JC Jr. The effect of the brain-type natriuretic peptide single-nucleotide polymorphism rs198389 on test characteristics of common assays. Mayo Clin Proc. 2011;86(3):210-218. PubMed, PubMedCentral, CrossRef
  19. Al-Gazally ME, Al-Awad AS, Kzar HH. Evaluating the Superoxide Dismutase-1 status in Wild Type and Mutant at codons 12 and 13 of KRAS gene Spectrum for the Patients with Sporadic Colorectal Cancer. Int J PharmTech Res. 2016;9(3):272-279.
  20. Sudoh T, Maekawa K, Kojima M, Minamino N, Kangawa K, Matsuo H. Cloning and sequence analysis of cDNA encoding a precursor for human brain natriuretic peptide. Biochem Biophys Res Commun. 1989;159(3):1427-1434. PubMed, CrossRef
  21. Zhang H, Li X, Zhang N, Tian L. Effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide levels: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:1083171. PubMed, PubMedCentral, CrossRef
  22. Turić I, Velat I, Bušić Ž, Čulić V. Circulating thyroid hormones and clinical parameters of heart failure in men. Sci Rep. 2023;13(1):20319. PubMed, PubMedCentral, CrossRef
  23. Karabag T, Dogan SM, Bayraktaroğlu T, Sayin MR, Buyukuysal C, Akpinar I, Aydin M. Assessment of left atrial mechanical functions in thyroid dysfunction. Pol Arch Med Wewn. 2013;123(11):596-602. PubMed, CrossRef
  24. Yang Y, Zmuda JM, Wojczynski MK, Thyagarajan B, Christensen K, Cvejkus RK, Kuipers AL. Genetic association analysis of the cardiovascular biomarker: N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). PLoS One. 2021;16(3):e0248726. PubMed, PubMedCentral, CrossRef
  25. Musani SK, Fox ER, Kraja A, Bidulescu A, Lieb W, Lin H, Beecham A, Chen MH, Felix JF, Fox CS, Kao WH, Kardia SL, Liu CT, Nalls MA, Rundek T, Sacco RL, Smith J, Sun YV, Wilson G, Zhang Z, Mosley TH, Taylor HA, Vasan RS. Genome-wide association analysis of plasma B-type natriuretic peptide in blacks: the Jackson Heart Study. Circ Cardiovasc Genet. 2015;8(1):122-130. PubMed, PubMedCentral, CrossRef
  26. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. ACC Curr J Rev. 2003;12(1):44. CrossRef
  27. Kautzky-Willer A. Sex and Gender Differences in Endocrinology. In: Oertelt-Prigione, S., Regitz-Zagrosek, V. (eds) Sex and Gender Aspects in Clinical Medicine. Springer, London. 2012: 125-149. CrossRef
  28. Park SB, Choi HC, Joo NS. The relation of thyroid function to components of the metabolic syndrome in Korean men and women. J Korean Med Sci. 2011;26(4):540-545. PubMed, PubMedCentral, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.