Povezanost polimorfizama gena za serotoninske 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C I 5-HT6 receptore u oboljelih od shizofrenije i akutnih ekstrapiramidalnih nuspojava antipsihotika haloperidola

doctoral thesis

• Title (english): The association between serotonin receptor 5-HT1A, 5 HT1B, 5-HT2A, 5-HT2C and 5-HT6 gene polymorphisms and acute extrapyramidal side effects in haloperidol-treated patients with schizophrenia
• Author: Mirko Grubor
• Mentor: Dubravka Švob Štrac (mentor)
• Mentor: Lidija Bach-Rojecky (komentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Nada Božina (član povjerenstva)
• Committee member: Sanja Dabelić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2020-10-26, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Uvod: Shizofrenija je kronični psihijatrijski poremećaj koji zahtijeva cjeloživotno liječenje.
Ekstrapiramidalne nuspojave (EPS) česte su nuspojave antipsihotičkih lijekova. Uz dopaminergički sustav,
u razvoj EPS-ova mogu biti uključeni i serotonergički mehanizmi putem serotoninskih (5-HT) receptora.
Svrha rada: Istražiti povezanost polimorfizama gena HTR1A, HTR1B, HTR2A, HTR2C i HTR6 s akutnim
EPS-ovima u bolesnika sa shizofrenijom nakon terapije haloperidolom.
Medode i ispitanici: Simpson Angusova ljestvica za EPS-ove (SAS), Barnesova ljestvica za akatiziju
(BARS) i Ljestvica za ocjenu EPS simptoma (ESRS) korištene su za procjenu težine EPS-ova nakon
dvotjedne terapije haloperidolom u 229 muškaraca s dijagnozom shizofrenije prema DSM-IV kriterijima.
Genotipizacija je provedena lančanom reakcijom polimeraze u stvarnom vremenu, nakon izolacije DNA iz
krvi.
Rezultati: Značajne akutne EPS-ove prijavilo je 48,03 % bolesnika sa shizofrenijom. Nositelji TT genotipa
HTR1B rs13212041 polimorfizma razvili su simptome akatizije nakon terapije haloperidolom učestalije i u
težem obliku od nositelja CT genotipa i C alela. Primjećene su i značajne razlike između nositelja CC i CT
genotipova HTR2A rs6313 polimorfizma u broju ESRS bodova za rigidnost, te između nositelja CC i TT
genotipova HTR6 rs1805054 polimorfizma u broju SAS i ESRS bodova za tremor. HTR2C rs3813929-
rs518147 haplotip TG bio je češći u bolesnika bez akutnih EPS-ova nego u bolesnika s akutnim EPS-ovima
nakon terapije haloperidolom.
Zaključak: Rezultati upućuju na genotipsku i haplotipsku povezanost pojedinih polimorfizama HTR1B,
HTR2A, HTR2C i HTR6 gena s akutnim EPS-ovima izazvanim primjenom haloperidola u oboljelih od
shizofrenije.

Abstract (english)

Backgorund: Schizophrenia is chronic psychiatric disorder requiring lifelong treatment. Extrapyramidal side
effects (EPS) are common adverse drug reactions of antipsychotics. In addition to the dopaminergic system,
serotonergic mechanisms via serotonin (5-HT) receptors might be also involved in the development of EPS.
Aim of study: The aim of the study was to examine the associations of HTR1A, HTR1B, HTR2A, HTR2C
and HTR6 gene polymorphisms with acute EPS in schizophrenia patients following haloperidol therapy.
Methods and patients: Simpson Angus Rating Scale for EPS (SAS), Barnes Akathisia Rating Scale (BARS)
and EPS Rating Scale (ESRS) were used to evaluate EPS severity in 229 schizophrenia-diagnosed males
(DSM-IV criteria). Genotyping was performed using Real-Time PCR following extraction of blood DNA.
Results: Significant acute EPS appeared in 48,03 % of schizophrenia patients. In the case of HTR1B
rs13212041 polymorphism, carriers of TT genotype developed akathisia more often and with more severe
symptoms following haloperidol therapy then carriers of CT genotype and C allele. Significant differences
were observed between carriers of CC and CT genotypes of HTR2A rs6313 polymorphism in the number of
ESRS scores for rigidity, and between carriers of CC and TT genotypes of HTR6 rs1805054 polymorphism
in the number of SAS and ESRS scores for tremor. The HTR2C rs3813929-rs518147 TG haplotype was more
frequent in patients without acute EPS than in patients who developed acute EPS after haloperidol therapy.
Conclusion: Results suggest the genotypic and haplotypic association of selected polymorphisms in HTR1B,
HTR2A, HTR2C and HTR6 genes with haloperidol-induced acute EPS in patients with schizophrenia.

• Keywords: shizofrenija; haloperidol; akutne ekstrapiramidalne nuspojave; serotoninski receptori; polimorfizmi; HTR1A gen; HTR1B gen; HTR2A gen; HTR2C gen; HTR6 gen
• Keywords (english): schizophrenia; haloperidol; acute extrapyramidal side effects; serotonin receptors; polymorphisms; HTR1A gene; HTR1B gene; HTR2A gene; HTR2C gene; HTR6 gene
• Language: croatian
• URN:NBN: urn:nbn:hr:163:144566
• Promotion: 2021
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-05-19 08:52:35