Title Identifikacija genetskih i okolišnih čimbenika uključenih u regulaciju funkcije štitne i doštitne žlijezde Title (english) Identification of genetic and environmental factors involved in the regulation of thyroid and parathyroid glands function Author Antonela Matana Mentor Tatijana Zemunik (mentor)Committee member Janoš Terzić (predsjednik povjerenstva)Committee member Irena Drmić-Hofman (član povjerenstva)Committee member Floriana Bulić-Jakuš Granter University of Split Defense date and country 2018, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Uvod: Paratireoidni hormon (PTH) je najvažniji čimbenik u regulaciji izvanstanične
koncentracije kalcija. Tireoidna peroksidaza (TPO) i tireoglobulin (Tg) su glavne sastavnice
štitne žlijezde koje igraju ključnu ulogu u sintezi hormona štitne žlijezde. Povišena razina
protutijela protiv TPO (TPO-At) i/ili Tg (Tg-At) može predstavljati ranu fazu u patogenezi
autoimunih bolesti štitnjače. Razine PTH, TPO-At i Tg-At rezultat su interakcije između
multiplih gena i jednako važnih čimbenika okoliša. Cilj ovog istraživanja bio je identificirati
nove genetske čimbenike povezane s razinom PTH, Tg-At i TPO-At te ispitati povezanost
prehrambenih navika, kao okolišnog čimbenika, s pozitivnim Tg-AT i/ili TPO-AT.
Metode: Istraživanje se provelo na ispitanicima koji su uključeni u projekt „10 001
Dalmatinac – Hrvatska biobanka“. U genetičkom dijelu istraživanju sudjelovalo je 2 869
ispitanika s područja grada Splita te otoka Korčule i Visa. Cjelogenomske analize povezanosti
provedene su korištenjem linearnog mješovitog modela, s prilagodbom za dob, spol i srodstvo
ispitanika. U istraživanju povezanosti prehrambenih navika s pozitivnim Tg-At i/ili TPO-At
sudjelovalo je ukupno 1887 subjekata (462 ispitanika i 1 425 kontrola). Početni skup od 58
analiziranih namirnica reduciran je faktorskom analizom na 19 ključnih prehrambenih faktora.
Povezanost prehrambenih faktora s pozitivnim Tg-At i/ili TPO-At testirana je logističkom
regresijom.
Rezultati: Identificiran je lokus u blizini gena RASGEF1B, te je dodatno na pod-uzorku žena
identificiran i lokus unutar gena DPP10, za povezanost s razinom PTH. Nadalje,
bivarijantnom analizom na pod-uzorku žena identificiran je lokus u blizini gena GRIN3A za
povezanost s Tg-At i TPO-At. Isti lokus je pokazao graničnu povezanost s razinom TPO-At
na pod-uzorku žena, dok je lokus smješten pokraj gena DLL1 pokazao graničnu povezanost s
razinom Tg-At, također na pod-uzorku žena. U analizi povezanosti namirnica s pozitivnim
nalazom Tg-At i/ili TPO-At, pokazano je da je česta konzumacija životinjskih masti i maslaca
povezana s pozitivnim Tg-At i/ili TPO-At, dok je česta konzumacija povrća te sušenog voća,
oraha i orašastih proizvoda te mueslia povezana s negativnim nalazima Tg-At i/ili TPO-At.
Zaključak: Nova saznanja mogu pomoći u razumijevanju temeljnih bioloških putova
povezanih s funkcijom doštitne i štitne žlijezde te pružiti dodatne spoznaje relevantne za
kliničku primjenu.
Abstract (english) Introduction: Parathyroid hormone (PTH) is one of the principal regulators of calcium
homeostasis. Thyroglobulin (Tg) and thyroid peroxidise (TPO) are a major components of the
thyroid gland, both engaged in the production of thyroid hormones. The presence of
autoantibodies with specifity for Tg (TgAb) and TPO (TPOAb) might represent an early stage
in autoimmune thyroid diseases. PTH, TgAb and TPOAb levels are complex traits influenced
by a combination of genetic and environmental factors. The aim of this study was to identify
novel genetic loci associated with PTH, TgAb and TPOAb levels and evaluate the association
of dietary factors, as an environmental factor, with positive findings of TPOAb and/or TgAb.
Methods: The study was carried-out on samples obtained through the “10,001 Dalmatians”
project. The genetic analyses included 2 869 individuals originating from the city of Split and
the islands of Korčula and Vis. Genome-wide association analyses were performed using
linear mixed model, with adjustments for age, gender and relatedness among participants.
A total of 1887 subjects (462 cases and 1 425 controls) were enrolled to test the association
between dietary factors and positive findings of plasma TPOAb and TgAb. Principal
component analysis was used to reduce the initial list of 58 food items to 19 key dietary
groups (factors). We used logistic regression analysis to examine dietary factors associated
with positive TPOAb and/or TgAb.
Results: We identified a novel locus associated with plasma PTH level near RASGEF1B
gene. We also identified sex-specific association in females in DPP10 gene. Furthermore, the
bivariate analysis of TgAb and TPOAb in females revealed an association for the locus near
GRIN3A. The same locus showed borderline association with TPOAb levels in females. Also,
a novel locus near DLL1 gene showed borderline significance in association with TgAb levels
in females. Frequent consumption of animal fats and butter was associated with positive
plasma TPOAb and/or TgAb, while vegetables, dried fruit, nuts and muesli were associated
with negative findings of TPOAb and/or TgAb.
Conclusions: New findings can help in understanding the biological pathways involved in
thyroid and parathyroid function and provide the additional knowledge relevant for the
clinical practice.
Keywords
štitnjača
paratireoidne žlijezde
paratiroidni hormon
studija povezanosti genoma
Keywords (english)
Thyroid Gland
Parathyroid Glands
Parathyroid Hormone
Genome-Wide Association Study
Language croatian URN:NBN urn:nbn:hr:171:835823 Project Number: IP-2013-11-1498 Study programme Title: Translational Research in Biomedicine - TRIBE Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-05-11 10:49:12
