Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Psychiatry (São Paulo. 1999. Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462015000300008 |
Resumo: | 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. 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. 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). 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. |
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Brazilian Journal of Psychiatry (São Paulo. 1999. Online) |
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Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmissionEndophenotypepsychosisgeneticsdopamineexecutive function 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. 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. 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). 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.Associação Brasileira de Psiquiatria2015-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462015000300008Brazilian Journal of Psychiatry v.37 n.3 2015reponame:Brazilian Journal of Psychiatry (São Paulo. 1999. Online)instname:Associação Brasileira de Psiquiatria (ABP)instacron:ABP10.1590/1516-4446-2014-1553info:eu-repo/semantics/openAccessLoch,Alexandre A.van de Bilt,Martinus T.Bio,Danielle S.Prado,Carolina M. doSousa,Rafael T. deValiengo,Leandro L.Moreno,Ricardo A.Zanetti,Marcus V.Gattaz,Wagner F.eng2019-12-06T00:00:00Zoai:scielo:S1516-44462015000300008Revistahttp://www.bjp.org.br/ahead_of_print.asphttps://old.scielo.br/oai/scielo-oai.php||rbp@abpbrasil.org.br1809-452X1516-4446opendoar:2019-12-06T00:00Brazilian Journal of Psychiatry (São Paulo. 1999. Online) - Associação Brasileira de Psiquiatria (ABP)false |
dc.title.none.fl_str_mv |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
title |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
spellingShingle |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission Loch,Alexandre A. Endophenotype psychosis genetics dopamine executive function |
title_short |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
title_full |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
title_fullStr |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
title_full_unstemmed |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
title_sort |
Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission |
author |
Loch,Alexandre A. |
author_facet |
Loch,Alexandre A. van de Bilt,Martinus T. Bio,Danielle S. Prado,Carolina M. do Sousa,Rafael T. de Valiengo,Leandro L. Moreno,Ricardo A. Zanetti,Marcus V. Gattaz,Wagner F. |
author_role |
author |
author2 |
van de Bilt,Martinus T. Bio,Danielle S. Prado,Carolina M. do Sousa,Rafael T. de Valiengo,Leandro L. Moreno,Ricardo A. Zanetti,Marcus V. Gattaz,Wagner F. |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Loch,Alexandre A. van de Bilt,Martinus T. Bio,Danielle S. Prado,Carolina M. do Sousa,Rafael T. de Valiengo,Leandro L. Moreno,Ricardo A. Zanetti,Marcus V. Gattaz,Wagner F. |
dc.subject.por.fl_str_mv |
Endophenotype psychosis genetics dopamine executive function |
topic |
Endophenotype psychosis genetics dopamine executive function |
description |
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. 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. 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). 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. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-09-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462015000300008 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462015000300008 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1516-4446-2014-1553 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Psiquiatria |
publisher.none.fl_str_mv |
Associação Brasileira de Psiquiatria |
dc.source.none.fl_str_mv |
Brazilian Journal of Psychiatry v.37 n.3 2015 reponame:Brazilian Journal of Psychiatry (São Paulo. 1999. Online) instname:Associação Brasileira de Psiquiatria (ABP) instacron:ABP |
instname_str |
Associação Brasileira de Psiquiatria (ABP) |
instacron_str |
ABP |
institution |
ABP |
reponame_str |
Brazilian Journal of Psychiatry (São Paulo. 1999. Online) |
collection |
Brazilian Journal of Psychiatry (São Paulo. 1999. Online) |
repository.name.fl_str_mv |
Brazilian Journal of Psychiatry (São Paulo. 1999. Online) - Associação Brasileira de Psiquiatria (ABP) |
repository.mail.fl_str_mv |
||rbp@abpbrasil.org.br |
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1754212556844564480 |