Naslovna  > Nastava > Katedre > Medicinska biologija > ZNANOST > HRZZ istraživački projekti prof. Zemunik > Reguliranje funkcije štitne i doštitne žlijezde i homeostaze kalcija u krvi

Publicirani rezultati naše istraživačke skupine predstavljaju prve identificirane genetske varijante za većinu hormona/antitijela štitne žlijezde. Udio objašnjene genetske varijance za hormon doštitne žlijezde (PTH) iznosi samo 5,34 % dok za kalcitonin i osteokalcin koji zajedno s PTH reguliraju homeostazu kalcija u krvi nema provedenih cjelogenomskih studija do sada. Predikcijske analize poprimaju sve veći značaj u posljednjih nekoliko godina. Cilj takvih analiza je predviđanje vrijednosti kvantitativnog svojstva baziranog na zajedničkom učinku genetičkih i okolišnih čimbenika. Ovakav tip analiza nije primijenjen za predviđanje razine hormona/antitijela štitne žlijezde, kao ni za parametre koju reguliraju homeostazu kalcija u krvi. Stoga su prva dva cilja predloženog projekta povećanje udjela objašnjene genetske varijance za hormone/antitijela štitne žlijezde i parametara regulacije homeostaze kalcija u krvi i predikcija istih bazirana na genetičkim i okolišnim čimbenicima. Istraživanje će biti provedeno na 2.000 ispitanika (populacije imenovane Korčula2, Korčula3), a rezultati će biti objedinjeni meta-analizom s prethodno dobivenim rezultatima na 3.000 ispitanika (populacije imenovane Split, Korčula1, Vis) za hormone i antitijela štitne i doštitne žlijezde, dok će analize za vrijednosti kalcitonina i osteokalcina biti provedene po prvi put na ukupno 5.000 ispitanika (u svim populacijama). Svi ispitanici regrutirani su iz projekta „10.001 Dalmatinac“ te raspolažemo genotipskim i nizom anamnestičkih i fenotipski mjerljivih podataka potrebnih za ove analize. Treći cilj projekta predstavlja funkcionalnu potvrdu identificiranih gena koji se povezuju s razinom tireoglobulina (Tg) i pozitivnim nalazom protutijela štitne žlijezde (TPOAt i/ili TgAt) u plazmi. Utvrdit će se razlika u ekspresiji dva gena u patološkom u odnosu na zdravo tkivo štitne žlijezde imunohistokemijskim metodama. Ovakva istraživanja preduvjet su razvoja personalizirane medicine.

 

Project summary:

First identified genetic variants for most thyroid hormones/antibodies have been recently published by our research group. For now, only 5.34% of genetic variance has been explained for parathyroid hormone (PTH) levels while calcitonin and osteocalcin, which together with PTH regulate blood calcium homeostasis, have not been analysed on a genome-wide level. Prediction analyses have gained increasing significance over the last few years. The aim of such analyses is to predict the value of a quantitative trait based on genetic and environmental parameters. These analyses have not been performed in the prediction of thyroid hormones/antibodies levels or blood calcium homeostasis parameters. Therefore, the first two goals of the proposed project are increasing the amount of explained genetic variance of thyroid complex phenotypes and parameters of calcium homeostasis, and their prediction based on identified genetic variants and environmental factors. The analysis of thyroid hormones/antibodies will be performed in 2.000 participants (populations named Korčula2, Korcula3), and the results will be meta-analyzed with previously obtained results of 3.000 participants (populations named Split, Korcula1, Vis). Analyses of calcitonin and osteocalcin will be performed in a total of 5.000 participants (in all populations), for the first time. All participants are recruited through the project „10.001 Dalmatians“ and have genotypic and a series of anamnestic and phenotypic data needed for these analyses. The third project goal is based on the best results of our previous project and represents the functional studies of genes identified to be associated with thyroglobulin (Tg) plasma levels and positive antibody (TPOAb and/or TgAb) findings. It is planned to establish the difference in the gene expression between pathological and healthy thyroid tissue using immunohistochemical methods. Such studies are a prerequisite for the development of personalized medicine.

Projekt razvoja karijera mladih istraživača-izobrazba novih doktora znanosti

Plan razvoja karijere doktoranda

Znanstveni radovi:

1. Sterenborg RBTM, Steinbrenner I, Li Y,...Gunjača I.,…Punda A.,..Zemunik T. et al. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications. Nat Commun. 2024;15(1):888. Published 2024 Jan 30. doi:10.1038/s41467-024-44701-9
2. Pleić N, Gunjača I, Babić Leko M, Zemunik T. Thyroid function and metabolic syndrome: a two-sample bidirectional Mendelian randomization study. J Clin Endocrinol Metab. 2023 Jun 20:dgad371. doi: 10.1210/clinem/dgad371.
3. Gunjača I, Benzon B, Pleić N, Babić Leko M, Pešutić Pisac V, Barić A, Kaličanin D, Punda A, Polašek O, Vukojević K, Zemunik T. Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets. Int J Mol Sci. 2023;24:16334. doi: 10.3390/ijms242216334
4. Zemunik T, Babić Leko M, Gunjača I. Editorial: Genetics of thyroid gland. Front Genet. 2023 May 30;14:1219472. doi: 10.3389/fgene.2023.1219472. eCollection 2023. 
5. Babić Leko M, Jureško I, Rozić I, Pleić N, Gunjača I, Zemunik T. Vitamin D and the Thyroid: A Critical Review of the Current Evidence. Int J Mol Sci. 2023 Feb 10;24(4):3586. doi: 10.3390/ijms24043586.
6. Babić Leko M, Pleić N, Lešin M, Gunjača I, Torlak V, Škunca Herman J, Vatavuk Z, Punda A, Polašek O, Hayward C, Zemunik T. Association between Thyroid Function and Ocular Parameters. Biology (Basel). 2022 Dec 18;11(12):1847. doi: 10.3390/biology11121847.
7. Babić Leko M, Nikolac Perković M, Španić E, Švob Štrac D, Pleić N, Vogrinc Ž, Gunjača I, Bežovan D, Nedić Erjavec G, Klepac N, Borovečki F, Zemunik T, Pivac N, Hof PR, Šimić G. Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer's Disease. Biomedicines. 2022 Dec 2;10(12):3118. doi: 10.3390/biomedicines10123118
8.  Pleić N, Brdar D, Gunjača I, Babić Leko M, Torlak V, Punda A, Polašek O, Hayward C, Zemunik T. Thyroid Hormones Are Not Associated with Plasma Osteocalcin Levels in Adult Population with Normal Thyroid Function. Metabolites 2022, 4;12:719. doi: 10.3390/metabo12080719
9. Strikić Đula I, Pleić N, Babić Leko M, Gunjača I, Torlak V, Brdar D, Punda A, Polašek O, Hayward C, Zemunik T. Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population. Biology 2022, 11, 394. https://doi.org/10.3390/biology11030394 
10. Pleić N, Babić Leko M, Gunjača I, Boutin T, Torlak V, Matana A, Punda A, Polašek O, Hayward C, Zemunik T. Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels. Int. J. Mol. Sci. 2022, 23, 2173. https://doi.org/10.3390/ijms23042173 
11. Babić Leko M, Pleić N, Gunjača I, Zemunik T. Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels. Int J Mol Sci. 2021 Dec 21;23(1):44. doi: 10.3390/ijms23010044. 
12. Brdar D*, Gunjača I*, Pleić N, Torlak V, Knežević P, Punda A, Polašek O, Hayward C, Zemunik T. The effect of food groups and nutrients on thyroid hormone levels in healthy individuals. Nutrition 2021;91-92:111394. doi: 10.1016/j.nut.2021.111394.
13. Babić Leko M, Gunjača I, Pleić N, Zemunik T. Environmental Factors Affecting Thyroid-Stimulating Hormone and Thyroid Hormone Levels. Int J Mol Sci 2021;22:6521. doi: 10.3390/ijms22126521.
14. Punda A, Škrabić V, Torlak V, Gunjača I, Boraska Perica V, Kolčić I, Polašek O, Hayward C, Zemunik T, Matana A. Thyroid hormone levels are associated with metabolic components: a cross-sectional study. Croat Med J. 2020; 61:230-238. doi: 10.3325/cmj.2020.61.230
15. Zemunik T, Gunjača I, Torlak V, Škrabić R, Vujičević M, Barić A, Vuletić M, Škrabić V, Punda A, Matana A. Determinants of thyroid volume in healthy young adults of Dalmatia. Periodicum Biologorum. 2020; 121-122(1-2), 65-69, doi: 10.18054/pb.v121-122i1-2.10268

Kongresna priopćenja:
 

1. Zemunik T, Pleic N, Gunjača I, Babić Leko M. Mendelian randomization shows no causal effect of serum vitamin D levels on thyroid function. ASHG annual meeting. Washington DC, USA, studeni 2023 (Poster prezentacija)
2. Pleic N, Zemunik T, Gunjača I, Babić Leko M. Thyroid function and metabolic syndrome: a two-sample bidirectional Mendelian randomization study. ASHG annual meeting. Washington DC, USA, studeni 2023 (Poster prezentacija).
3. Pleić N, Gunjača I, Babić Leko M, Zemunik T. Thyroid function and metabolic syndrome: a two-sample bidirectional Mendelian randomization study. 26th International Scientific Symposium on Biometrics (BIOSTAT), Zadar, Croatia, lipanj 2023 (Usmeno priopćenje). 
4. Zemunik T, Pleić N, Gunjača I, Babić Leko M, Boutin T, Torlak V, Punda A, Polašek O, Hayward C. Genome-wide association analysis of plasma osteocalcin levels in European-ancestry participants of the Croatian Biobank. 14th International Congress of Human Genetics (ICHG), Cape Town, South Africa, veljača 2023 (Poster prezentacija). 
5. Pleić N, Babić Leko M, Gunjača I, Boutin T, Torlak V, Punda A, Polašek O, Hayward C, Zemunik T. Genome-wide association analysis reveals novel insights into the genetic architecture of plasma calcitonin levels. 14th International Congress of Human Genetics (ICHG), Cape Town, South Africa, veljača 2023 (Poster prezentacija).
6. Babić Leko M, Pleić N, Lešin M, Gunjača I, Torlak V, Punda A, Polašek O, Zemunik T. Association of optical parameters with TSH, thyroid hormones and thypoglobulin levels. Congress of the Croatian Society of Biochemistry and Molecular Biology, HDBMB22, Brela, rujan do listopad 2022 (Poster prezentacija).
7. Zemunik T, Pleić N, Babić Leko M, Gunjača I, Torlak V, Punda A, Polašek O, Boutin T, Hayward C. Genome-wide meta-analysis identfes novel loci for positve thyroid peroxidase and thyroglobulin antbodies. European Human Genetics Conference, Beč, lipanj 2022 (Poster prezentacija).
8. Pleić N, Babić Leko M, Gunjača I, Boutin T, Torlak V, Matana A, Punda A, Polašek O, Hayward C, Zemunik T. Genome-wide association analysis and genomic prediction of thyroglobulin plasma levels. European Human Genetics Conference, Beč, lipanj 2022 (Poster prezentacija).
9. Gunjača I, Benzon B, Babić Leko M, Pleić N, Pešutić Pisac V, Barić A, Punda A, Polašek O, Vukojević K, Zemunik T. Expression of ST6GAL1 protein in thyroid cancers. European Human Genetics Conference, Beč, lipanj 2022 (Poster prezentacija).
10. Babić Leko M, Pleić N, Gunjača I, Torlak V, Punda A, Šimić G, Polašek O, Zemunik T. The association of TSH and thyroid hormones with APOE genotype. 8th Mediterranean Society Conference Croatia MNS2022, Baška Voda, svibanj-lipanj 2022 (Poster prezentacija).
11. Pleić N, Gunjača I, Babić Leko M, Polašek O, Zemunik T. Comparing parametric and non-parametric Bayesian approaches for genetic prediction of complex traits. 4^th International Statistical Conference in Croatia, Opatija, travanj 2022 (Usmeno izlaganje)
12. Pleić N, Boutin T, Gunjača I, Babić Leko M, Torlak V, Matana A, Punda A, Polašek O, Hayward C, Zemunik T. Genome-wide meta-analysis of thyroglobulin plasma level in healthy individuals provides evidence for replication of 16 and identification of 68 novel loci within ST6GAL1 gene. Simpozij mladih znanstvenika, Medicinski fakultet Split, lipanj 2021 (Usmeno izlaganje)
13. Zemunik T, Gunjača I, Torlak V, Vujičević M, Barić A, Vuletić M, Škrabić V, Punda A, Matana A. Determinants of thyroid volume in healthy young adults of Dalmatia. 10^th International Congress of the Croatian Society of Nuclear Medicine, Vodice, rujan 2021 (Poster prezentacija)

Obrane doktorata:
Dr. Ivana Strikić Đula obranila je doktorsku disertaciju pod naslovom: „Epidemiologija hipotireoze, hipertireoze i prisustva pozitivnih protutijela štitnjače u Južnoj Hrvatskoj", Medicinski fakultet Split, 19. rujna 2023. (mentor: prof. dr. sc. Tatijana Zemunik)
 
Dr. Dubravka Brdar obranila je doktorsku disertaciju pod naslovom: „Utjecaj prehrane na razinu hormona štitne žlijezde u plazmi i njihova uloga u pregradnji kostiju“ Medicinski fakultet Split, 20. prosinca 2022. (mentor: prof. dr. sc. Tatijana Zemunik)

Diplomski radovi:
1. Petra Knežević: Utjecaj prehrane na hormonski status štitne žlijezde. Diplomski rad. Integrirani preddiplomski i diplomski studij farmacije, Medicinski fakultet Split, obranjen 22. listopada 2020. (mentor prof. dr. sc. Tatijana Zemunik)

2. Marina Vujičević: Određivanje parametara koji utječu na volume štitne žlijezde. Integrirani preddiplomski i diplomski studij farmacije, Medicinski fakultet Split, obranjen 22. siječnja 2021. (mentor prof. dr. sc. Tatijana Zemunik)


Nagrade i priznanja:

Promocija znanosti

Nikolina Pleić mag. math. sudjelovala je 9. veljače 2024. u Vijećnici Prirodoslovno-matematičkog fakulteta, u okruglom stolu na temu "Žene u STEMu" u organizaciji Fizikalnog društva Split, a povodom Međunarodnog dana žena i djevojaka u znanosti.
Link: https://www.linkedin.com/events/okruglistol-eneustemu7160225740376944641/about/ 

Nikolina Pleić mag. math. i dr. sc. Ivana Gunjača sudjelovale su u popularizaciji znanosti kroz intervju na službenoj radio stanici Sveučilišta u Splitu - Radio Kampus.
Link: https://www.linkedin.com/posts/nikolinapleic_mefst-gwas-unist-activity-7122890845481033729-Wgit?utm_source=share&utm_medium=member_desktop

Istraživački tim sudjelovao je u promociji znanosti i promociji projekta kroz objavu članka u hrvatskim sveučilišnim novinama Universitas. Članak je također objavljen i na stranicama Slobodne Dalmacije.
Link: https://slobodnadalmacija.hr/split/mladi-strazivaci-sa-splitske-medicine-dosli-do-velikog-otkrica-prvi-su-dokazali-povezanost-ovih-dviju-ucestalih-bolesti-1327112