The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: systematic review and meta-analysis

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Abstract

Background

The association between the dopamine D2 receptor ( DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study was to perform a systematic review and meta-analysis to explore the relation between three polymorphisms of the DRD2 gene (C957T, TaqI and Ser311Cys) and schizophrenia.

Methods

The search was made in PubMed and EBSCO databases (up to February 2016). The systematic review included 34 case–control association studies (34 for C957T, 16 for TaqI and 36 for Ser311Cys). The association analysis comprised the allelic, additive, dominant, and recessive genetic models. The meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.

Results

The meta-analysis showed that TaqI (additive model: OR 0.57, 95% CI 0.30–1.14) and C957T (additive model: OR 0.75, 95% OR 0.58–0.97, recessive model: OR 0.79, 95% CI 0.64–0.98) exert a protective effect against developing schizophrenia. However, the sub-analysis for the C957T variant showed that this polymorphism exhibits a risk factor effect on Chinese individuals (allelic model: OR 1.33, 95% CI 1.04–1.70).

Conclusion

Our meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.

Electronic supplementary material

The online version of this article (doi:10.1186/s12993-016-0114-z) contains supplementary material, which is available to authorized users.

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Most cited references 82

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How Schizophrenia Develops: Cognitive and Brain Mechanisms Underlying Onset of Psychosis.

Tyrone Cannon (2015)

Identifying cognitive and neural mechanisms involved in the development of schizophrenia requires longitudinal observation of individuals prior to onset. Here recent studies of prodromal individuals who progress to full psychosis are briefly reviewed in relation to models of schizophrenia pathophysiology. Together, this body of work suggests that disruption in brain connectivity, driven primarily by a progressive reduction in dendritic spines on cortical pyramidal neurons, may represent a key triggering mechanism. The earliest disruptions appear to be in circuits involved in referencing experiences according to time, place, and agency, which may result in a failure to recognize particular cognitions as self-generated or to constrain interpretations of the meaning of events based on prior experiences, providing the scaffolding for faulty reality testing.

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No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics.

David Crowe, Pablo Rozic, P V Gejman … (2008)

The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3' untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.

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The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.

B G Comings, D Tast, B Kovács … (1991)

--The A1 allele of the Taq I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. --Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. --Ambulatory and hospitalized patients. --Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring P less than .0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

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Author and article information

Contributors

Thelma Beatriz González-Castro: thelma.glez.castro@gmail.com

Yazmín Hernández-Díaz: yazmin.hdez.diaz@gmail.com

Isela Esther Juárez-Rojop: iselajuarezrojop@hotmail.com

María Lilia López-Narváez: dralilialonar@yahoo.com.mx

Carlos Alfonso Tovilla-Zárate: 52 9933581500 , alfonso_tovillaz@yahoo.com.mx

Alma Genis-Mendoza: adgenis@inmegen.gob.mx

Mariela Alpuin-Reyes: fareyesp@hotmail.com

Journal

Journal ID (nlm-ta): Behav Brain Funct

Journal ID (iso-abbrev): Behav Brain Funct

Title: Behavioral and Brain Functions : BBF

Publisher: BioMed Central (London )

ISSN (Electronic): 1744-9081

Publication date (Electronic): 9 November 2016

Publication date PMC-release: 9 November 2016

Publication date Collection: 2016

Volume: 12

Electronic Location Identifier: 29

Affiliations

[1 ]División Académica Multidisciplinaria de Jalpa de Méndez, Universidad Juárez Autónoma de Tabasco, Jalpa de Méndez, Tabasco Mexico

[2 ]División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco Mexico

[3 ]Secretaría de Salud, Hospital General de Yajalón, Yajalón, Chiapas Mexico

[4 ]División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Ranchería Sur, Cuarta Sección, C.P. 86650 Comalcalco, Tabasco Mexico

[5 ]Secretaría de Salud, Instituto Nacional de Medicina Genómica (INMEGEN), Servicios de Atención Psiquiátrica (SAP), Ciudad de México, Mexico

Article

Publisher ID: 114

DOI: 10.1186/s12993-016-0114-z

PMC ID: 5101652

PubMed ID: 27829443

SO-VID: a61374a6-5d2f-40db-943a-42b25bff5ebb

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 20 June 2016

Date accepted : 4 November 2016

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ScienceOpen disciplines: Neurology

Keywords: schizophrenia,drd2 gene,meta-analysis,systematic review,polymorphism

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ScienceOpen disciplines: Neurology

Keywords: schizophrenia, drd2 gene, meta-analysis, systematic review, polymorphism

The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: systematic review and meta-analysis

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Conclusion

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Karger: Neurology and Neuroscience

Most cited references 82

How Schizophrenia Develops: Cognitive and Brain Mechanisms Underlying Onset of Psychosis.

No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics.

The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.

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