Genotypic and Haplotypic Association of Catechol- O-Methyltransferase rs4680 and rs4818 Gene Polymorphisms with Particular Clinical Symptoms in Schizophrenia

Marina Sagud; Lucija Tudor; Gordana Nedic Erjavec; Matea Nikolac Perkovic; Suzana Uzun; Ninoslav Mimica; Zoran Madzarac; Maja Zivkovic; Oliver Kozumplik; Marcela Konjevod; Dubravka Svob Strac; Nela Pivac

doi:10.3390/genes14071358

Genotypic and Haplotypic Association of Catechol- O-Methyltransferase rs4680 and rs4818 Gene Polymorphisms with Particular Clinical Symptoms in Schizophrenia

Genes (Basel). 2023 Jun 27;14(7):1358. doi: 10.3390/genes14071358.

Authors

Marina Sagud^{1

2}, Lucija Tudor³, Gordana Nedic Erjavec³, Matea Nikolac Perkovic³, Suzana Uzun^{2

4}, Ninoslav Mimica^{2

4}, Zoran Madzarac¹, Maja Zivkovic¹, Oliver Kozumplik⁴, Marcela Konjevod³, Dubravka Svob Strac³, Nela Pivac^{3

5}

Affiliations

¹ Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia.
² School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
³ Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia.
⁴ Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, 10090 Zagreb, Croatia.
⁵ University of Applied Sciences Hrvatsko Zagorje Krapina, 49000 Krapina, Croatia.

Abstract

Catechol-O-methyl transferase (COMT) gene variants are involved in different neuropsychiatric disorders and cognitive impairments, associated with altered dopamine function. This study investigated the genotypic and haplotypic association of COMT rs4680 and rs4618 polymorphisms with the severity of cognitive and other clinical symptoms in 544 male and 385 female subjects with schizophrenia. COMT rs4818 G carriers were more frequent in male patients with mild abstract thinking difficulties, compared to CC homozygotes or C allele carriers. Male carriers of COMT rs4680 A allele had worse abstract thinking (N5) scores than GG carriers, whereas AA homozygotes were more frequent in male subjects with lower scores on the intensity of the somatic concern (G1) item, compared to G carriers. Male carriers of COMT rs4818-rs4680 GA haplotype had the highest scores on the G1 item (somatic concern), whereas GG haplotype carriers had the lowest scores on G2 (anxiety) and G6 (depression) items. COMT GG haplotype was less frequent in female patients with severe disturbance of volition (G13 item) compared to the group with mild symptoms, while CG haplotype was more frequent in female patients with severe then mild symptoms. These findings suggest the sex-specific genotypic and haplotypic association of COMT variants with a severity of cognitive and other clinical symptoms of schizophrenia.

Keywords: COMT; clinical symptoms; cognition; haplotype; polymorphisms; schizophrenia; sex-differences.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catechol O-Methyltransferase* / genetics
Female
Genotype
Haplotypes
Humans
Male
Polymorphism, Single Nucleotide
Schizophrenia* / genetics

Substances

Catechol O-Methyltransferase

Grants and funding

This research was partly supported by CRO-USA collaborative project Pivac 1463002/1463002U, and by the project “Predictors of treatment response in schizophrenia”, sponsored by University of Zagreb, project code: BM106.