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Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission.

Authors :
Loch AA
van de Bilt MT
Bio DS
Prado CM
de Sousa RT
Valiengo LL
Moreno RA
Zanetti MV
Gattaz WF
Source :
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) [Braz J Psychiatry] 2015 Jul-Sep; Vol. 37 (3), pp. 235-41.
Publication Year :
2015

Abstract

Objective: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.<br />Methods: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance.<br />Results: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001).<br />Conclusion: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

Details

Language :
English
ISSN :
1809-452X
Volume :
37
Issue :
3
Database :
MEDLINE
Journal :
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)
Publication Type :
Academic Journal
Accession number :
26376054
Full Text :
https://doi.org/10.1590/1516-4446-2014-1553