Genetic predictors of thyroid and parathyroid function and blood calcium homeostasis

Genetic predictors of thyroid and parathyroid function and blood calcium homeostasis

The aim of this study is to identify genetic loci that are associated with levels of thyroid/parathyroid hormones and antibodies that will advance our understanding of the genetic basis of their function and thus provide additional knowledge relevant to clinical outcomes.

Genetic predictors of thyroid and parathyroid function and blood calcium homeostasis

 Genetički prediktori funkcije štitne i doštitne
žlijezde i homeostaza Ca u krvi
Head of research group
 Prof Tatijana Zemunik 

Thyroid hormones affect different metabolic and developmental processes and regulate vital body functions. Thyroid diseases affect up to 10% of the general population creating an important public health problem. Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Proper calcium balance is crucial to the normal functioning of the heart, nervous system, kidneys and bones. Calcitonin (CT) is a protein hormone synthesized and secreted in humans primarily by parafollicular cells (C cells) in the thyroid gland. It acts to reduce calcium levels in the blood opposing the effects of PTH. Osteocalcin (OCN) is the most common non-
collagen protein in bones that has hormonal activity and affects the formation of bone tissue or bone remodeling. OCN is secreted exclusively by osteoblasts and is thought to play an important role in the regulation of metabolism. It is also involved in bone mineralization and calcium ion homeostasis.
Circulating concentrations of thyroid and parathyroid hormones/antibodies, CT and OCN are partially determined by genetic factors and partly by environmental factors and are considered as complex traits. However, genetic variants regulating their serum levels, as well as environmental factors, are not well established. The main goal of the conducted project (2014 - 2018) was to identify genetic loci that are associated with levels of thyroid/parathyroid hormones and antibodies in order to improve our understanding of the genetic basis of their function and thus provide additional knowledge relevant to clinical outcomes.
The published results of our research group represent the first identified genetic variants for most thyroid hormones / antibodies. For now, only 5.34% of genetic variance has been explained for PTH. However, 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 analyses will be performed in 5.000 participants (populations named Split, Vis, Korcula1, Korčula2, Korcula3). 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. A new step forward in this project will be 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.
Lead researcher: prof. Tatijana Zemunik
Funded by Croatian Science Foundation - HRZZ
Duration: March 2020. - March 2024.
Lead researcher: prof. Tatijana Zemunik 
Funded by Croatian Science Foundation - HrZZ
Duration: sept 2014 - sept 2018
Group members
Prof Tatijana Zemunik, PhD, lead researcher  [CV]
prof. Caroline Hayward, PhD, Senior scientist
prof. Valdi Pešutić Pisac, PhD, associate - researcher
prof. Ante Punda, PhD, associate - researcher
prof. Vesna Boraska Perica, PhD, associate - researcher
Assoc. prof. Maja Barbalić, PhD associate - researcher [CV]
Assist prof. Vesea Torlak, PhD associate - researcher [CV]
Assist prof. Antonela Matana. PhD, associate - researcher [CV]
Assist prof. Mladen Lešin, PhD, associate - researcher
Ivana Gunjača, PhD, associate - researcher
Dubravka Brdar, MD, associate - researcher [CV]
Dean Kaličanin, mag. MSc, associate - researcher
Mirjana Babić Leko, PhD, postdoctoral researcher
Nikolina Pleić, MSc, - doctoral student
Future directions 
We plan to expand research on the regulation of blood calcium homeostasis by measuring the concentration of vitamin D in plasma and determining the genetic variants that affect its level in our population. We also plan to expand the range of environmental factors that can correlate with all analyzed parameters and examine clinically relevant influences on glandular function and blood calcium regulation.

Interests and topics: thyroid function, parathyroid function, parameters of blood calcium homeostasis, calcitonin, osteocalcin, genetic variants, polymorphisms, genome-wide study, gene-environmental interaction, complex phenotypes, prediction
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