Title (srp)

Povezanost polimorfizma u genu za receptor vitamina D sa genskom predispozicijom i kliničkim parametrima obolelih od osteoartritisa velikih zglobova

Author

Vranić, Vladimir

Contributor

Šupić, Gordana, 1973-
Ristić, Branko, 1962-
Cvetković, Danijela, 1982-
Rančić, Nemanja, 1984-

Description (srp)

Uvod. Osteoartritis je degenerativna, hronična i ireverzibilna bolest koja pogađa milioneljudi širom sveta. Uzroci i mehanizmi osteoartritisa nisu do kraja razjašnjeni. Vitamin D jebitan faktor u metabolizmu kostiju. Njegovo delovanje posreduje vitamin D receptor, faktortranskripcije koji kontroliše ekspresiju gena, održavajući na taj način homeostazukalcijuma i fosfata. Hipoteza o vitaminu D je da igra ključnu ulogu u brojnim mišićnokoštanim bolestima, uključujući osteoartritis, a njegov nedostatak preovlađuje međupacijentima s osteoartritisom.Polimorfizmi gena za receptor vitamina D (VDR) mogli bi da igraju značajnu ulogu ugenetskoj predispoziciji i patogenezi osteoartritisa (OA), najčešćeg degenerativnogporemećaja zglobova kod ljudi.Cilj. Cilj ove doktorske disertacije bilo je utvrđivanje postojanja povezanosti izmeđupolimorfizama FokI, TaqI, ApaI i EcoRV u VDR genu s rizikom za nastanak i progresijuosteoartritisa u domaćoj populaciji. Urađen je veliki broj studija u vezi s efektima vitaminaD na patogenezu i progresiju osteoartritisa, kao i njegovom upotrebom kao terapeutskogsredstva. Do sada su studije dale kontroverzne rezultate i nije postignut konsenzus po tompitanju. Našim radom želimo da istražimo trenutne podatke o mogućoj ulozi vitamina D injegovog receptora u patogenezi osteoartritisa, i procenimo efikasnost suplementacijevitamina D kao terapijske strategije.Materijal i metode. Studijska grupa ispitanika je obuhvatila ukupno 94 pacijenta s OA, akontrolna grupa 100 zdravih, asimptomatskih osoba odgovarajuće polne i starosnedistribucije. Polimorfizmi FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) i EcoRV(rs4516035) u VDR genu su određivani pomoću metode PCR-a u realnom vremenu (Realtime PCR).Rezultati. Analiza prilagođenog odnosa šansi (OR) pokazala je da su polimorfizmi VDRTaqI i FokI značajno povezani s predispozicijom za OA (OR = 1,986, p = 0,001, odnosno OR= 1,561, p = 0,017). Analiza specifična za tip zglobova pokazala je da je polimorfizam VDRTaqI povezan s rizikom nastanka OA kuka (OR = 1,930, p = 0,005) i OA kolena (OR = 1,916,p = 0,028), dok je polimorfizam VDR FokI povezan s višim rizikom pojave OA kolena (OR =2,117, p = 0,012). Polimorfizmi VDR TaqI i FokI povezani su s pojavom trajnog bola (p =0,005, odnosno p = 0,027), dok je ApaI povezan s porodičnom istorijom OA (p = 0,004).Zaključak. Genetske varijante VDR FokI i TaqI bi mogle značajno doprinositi riziku zanastanak osteoartritisa, pojavi trajnog bola i potencijalno riziku za pojavu OA specifičnog zatip zgloba.

Description (srp)

-

Description (eng)

Introduction. Osteoarthritis is a degenerative, chronic and irreversible disease that affectsmillions of people around the world. The causes and mechanisms of osteoarthritis are notfully understood. Vitamin D is an important factor in bone metabolism. Its action ismediated by the vitamin D receptor, a transcription factor that controls gene expression,thus maintaining the homeostasis of calcium and phosphate. The vitamin D hypothesis isthat it plays a key role in a number of musculoskeletal diseases, including osteoarthritis,and its deficiency is prevalent among patients with osteoarthritis.Vitamin D receptor (VDR) gene polymorphisms could play a significant role in thesusceptibility and pathogenesis of osteoarthritis (OA), the most common degenerative jointdisorder in humans.Aim. The aim of the doctoral dissertation was to determine the association betweenpolymorphisms FokI, TaqI, ApaI and EcoRV in VDR gene, with risk for the onset andprogression of osteoarthritis in the local population. A large number of studies have beendone regarding the effects of vitamin D on the pathogenesis and progression ofosteoarthritis, as well as its use as a therapeutic agent. So far, studies have yieldedcontroversial results and no consensus has been reached on the issue. Our work aims toinvestigate current data on the possible role of vitamin D and its receptor in thepathogenesis of osteoarthritis and to evaluate the efficacy of vitamin D supplementation asa therapeutic strategy.Material and methods. The current study involved 94 OA patients, and 100 healthy,asymptomatic controls. VDR variants FokI (rs2228570), TaqI (rs731236), ApaI(rs7975232) and EcoRV (rs4516035) were genotyped using the TaqMan based Real-TimePCR.Results. Adjusted Odds Ratio (OR) analysis showed that VDR TaqI and FokIpolymorphisms are significantly associated with the susceptibility to OA (OR=1.986,p=0.001, and OR=1.561, p=0.017, respectively). The joint-specific analysis showed that VDRTaqI polymorphism was associated with a risk of hip OA (OR=1.930, p=0.005) and the kneeOA (OR=1.916, p=0.028), while VDR FokI polymorphism was associated with the higherrisk of knee OA (OR=2.117, p=0.012). VDR TaqI and FokI polymorphisms are associatedwith the occurrence of persistent pain (p=0.005, and p=0.027, respectively), while ApaIwas associated with a family history of OA (p=0.004).Conclusion. The VDR FokI and TaqI genetic variants significantly contribute toosteoarthritis susceptibility, the occurrence of persistent pain, and potentially to jointspecific OA risk.

Object languages

Serbian

Date

2022

Rights

Creative Commons License
This work is licensed under a
CC BY-ND 3.0 AT - Creative Commons Attribution-NoDerivs 3.0 Austria License.

http://creativecommons.org/licenses/by-nd/3.0/at/legalcode

Identifiers