Haplotypic and genotypic Association of catechol-O-methyltransferase rs4680 and rs4818 polymorphisms and treatment resistance in schizophrenia

Scientific paper - Original scientific paper

• Author: Marina Šagud
• Author: Lucija Tudor
• Author: Suzana Uzun
• Author: Matea Nikolas Perković
• Author: Maja Živković
• Author: Marcela Konjevod
• Author: Oliver Kozumplik
• Author: Bjanka Vuksan Ćusa
• Author: Dubravka Švob Štrac
• Author: Iva Radoš
• Author: Ninoslav Mimica
• Author: Alma Mihaljević Peleš
• Author: Gordana Nedić Erjavec
• Author: Nela Pivac
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to
different factors, including alterations in the activity of brain dopaminergic system, which
could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase
(COMT). Variants of the COMT gene have been extensively studied as risk factors
for schizophrenia; however, their association with TRS has been poorly investigated.
The aim of the present study was to determine the haplotypic and genotypic
association of COMT rs4680 and rs4818 polymorphisms with the presence of TRS.
Overall, 931 Caucasian patients diagnosed with schizophrenia (386 females and 545
males) were included, while 270 participants met the criteria for TRS. In males, no
significant haplotypic and genotypic associations between COMT rs4680 and rs4818
polymorphisms and TRS were detected. However, genotypic analyses demonstrated
higher frequency of COMT rs4680 AA genotype carriers compared to G-allele carriers
(p = 0.033) and higher frequency of COMT rs4818 CC genotype carriers than G-allele
carriers (p = 0.014) in females with TRS. Haplotype analyses confirmed that the
presence of the G allele in females was associated with lower risk of TRS. In women with
TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes
were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high activity
(G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females,
but not in males, suggest significant, but sex-specific influence of COMT variants on the
development of treatment-resistance in patients with schizophrenia. However, due to
relatively low number of females, those findings require replication in a larger sample.

• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Frontiers in Pharmacology
• Numbering: vol. 9, no. 705
• p-ISSN: 1663-9812
• DOI: https://doi.org/10.3389/fphar.2018.00705
• URN:NBN: urn:nbn:hr:105:769077
• Publication: 2018-07-03
• Document URL: https://doi.org/10.3389/fphar.2018.00705
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 10:06:53