Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders

doi:10.1016/0165-0327(96)00035-3

Journal of Affective Disorders

Volume 40, Issues 1–2, 9 September 1996, Pages 7-13

https://doi.org/10.1016/0165-0327(96)00035-3 Get rights and content

Abstract

Disturbances in dopaminergic systems have been implicated in the etiology of mood disorders. Although genetic factors also play an important role, no major gene has been identified. We conducted an association study using the dopamine D2, D3 and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that there is a significant association between the dopamine D4 receptor gene and mood disorders, especially major depression, but no association between the other polymorphisms and mood disorders. Further investigations are needed to clarify the clinical significance of this association in the pathophysiology of mood disorders.

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Association of DRD2 gene polymorphisms with mood disorders: A meta-analysis
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Citation Excerpt :
A P value of less than 0.05 was considered statistically significant, and all the P values were two sided. Characteristics of studies investigating the association of DRD2 gene polymorphisms with mood disorders are presented in Table 1 (Huuhka et al., 2008; Kõks et al., 2006; Leszczyńska-Rodziewicz et al., 2005; Cusin et al., 2002; Massat et al., 2002; Heiden et al., 2000; Gorwood et al., 2000; Li et al., 1999; Savoye et al., 1998; Furlong et al., 1998; Stöber et al., 1998; Golimbet et al., 1998; Manki et al., 1996; Sasaki et al., 1996; Arinami et al., 1996; Pérez de Castro et al., 1995; Craddock et al., 1995; Nöthen et al., 1992). There were 9523 papers relevant to the searching word (PubMed: 569; Elsevier Science Direct: 8416; Cochrane Library: 9; CBM: 15; CNKI: 294; and Wanfang: 22).
In the past few decades, a number of studies have investigated the association of dopamine D2 receptor (DRD2) gene polymorphisms with mood disorders, but the findings are not always consistent. The aim of our study was to assess the association between DRD2 gene polymorphisms and mood disorders by using a meta-analysis.
Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang, with the last report up to June 2010. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2.
We identified 19 separate studies using search, but only 14 separate studies (2157 cases and 3272 controls) were included in the current study. Meta-analysis was performed for three DRD2 gene polymorphisms (-141Cins/del, Ser311/Cys311, and TaqI A1). We performed meta-analysis in overall, Caucasian, and Asian populations. We also performed disease-specific meta-analysis in unipolar disorder and bipolar disorder. We found no association between DRD2 gene -141Cins/del polymorphism and mood disorders in overall and Caucasian populations (P > 0.05). We also found no association between DRD2 gene Ser311/Cys311 polymorphism and mood disorders in overall, Caucasian, and Asian populations (P > 0.05). An association of DRD2 gene TaqI A1 polymorphism with mood disorders was found in overall population, and the individuals with A1A1 genotype were more susceptible to mood disorders in comparison to those with A2A1 and A2A2 genotypes (OR = 1.84, 95% CI = 1.07–3.17, P = 0.03).
Meta-analysis is retrospective research that is subject to the methodological deficiencies of the included studies.
This meta-analysis suggests that mood disorders may be associated with DRD2 gene TaqI A1 polymorphism, but not -141Cins/del and Ser311/Cys311.
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Major depressive disorder (MDD) is a common psychiatric disorder and leading cause of disability worldwide. It is associated with increased mortality, especially from suicide. Heritability of MDD is estimated around 40%, suggesting that genotyping is a promising field for research into the development of MDD. According to the dopamine theory of affective disorders, a deficiency in dopaminergic neurotransmission may play a role in the major symptoms of MDD. Specific polymorphisms in genes that affect dopamine transmission could increase susceptibility to MDD. To determine the extent to which these genes influence vulnerability to MDD, we discuss genes for crucial steps in dopamine neurotransmission: synthesis, signalling and inactivation. The val158met polymorphism of the COMT gene exemplifies the lack of consensus in the literature: although it is one of the most reported polymorphisms that relates to MDD vulnerability, its role is not corroborated by meta-analysis. Gene–gene interactions and gene–environment interactions provide more explanatory potential than single gene associations. Two notable exceptions are the DRD4 and DAT gene: both have variable tandem repeat polymorphisms which may have a “single gene” influence on susceptibility to MDD.
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Research reportDopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders

Abstract

Lancet

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Lancet i

Genomics

Psychiatry Res.

Neuron

Genomics

Genomics

Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees

Nature Genet.

Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking

Nature Genet.

Approaches to the genetics of affective disorders

Ann. Med.

Nonlinkage of bipolar illness to tyrosine hydroxylase, tyrosinase, and D2 and D4 dopamine receptor genes on chromosome 11

Am. J. Psychiatry

Close linkage of c-Harvey-ras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees

Nature

Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking

Nature Genet.

Bipolar affective disorders linked to DNA markers on chromosome 11

Nature

Research report
Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders