A search for association between schizophrenia and dopamine-related alleles

Jönsson, Erik G.; Brené, Stefan; Geijer, Thomas; Terenius, Lars; Tylec, A.; Persson, Malin; Sedvall, Göran

doi:10.1007/bf02189022

Cited by 47 publications

(25 citation statements)

References 92 publications

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“…However, it was proved that the antipsychotic activity of clozapine cannot be merely explained by its combined serotonin/D4 receptor antagonist properties. Furthermore, many searches for possible associations between schizophrenia and the D4 gene polymorphism have not led to strong links [151,158,159], and genetic studies too have failed to demonstrate a correlation between D4 polymorphism and the clozapine response [160,161]. However, a lot of evidence supports the hypothesis that a reduction in positive symptoms following treatment with antipsychotics is mediated through blockade of D2 receptors.…”

Section: Dopamine-related Diseasesmentioning

confidence: 96%

The dopamine D4 receptor: biochemical and signalling properties

Rondou

Haegeman

Craenenbroeck

2010

Cell. Mol. Life Sci.

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Dopamine is an important neurotransmitter that regulates several key functions in the brain, such as motor output, motivation and reward, learning and memory, and endocrine regulation. Dopamine does not mediate fast synaptic transmission, but rather modulates it by triggering slow-acting effects through the activation of dopamine receptors, which belong to the G-protein-coupled receptor superfamily. Besides activating different effectors through G-protein coupling, dopamine receptors also signal through interaction with a variety of proteins, collectively termed dopamine receptor-interacting proteins. We focus on the dopamine D4 receptor, which contains an important polymorphism in its third intracellular loop. This polymorphism has been the subject of numerous studies investigating links with several brain disorders, such as attention-deficit hyperactivity disorder and schizophrenia. We provide an overview of the structure, signalling properties and regulation of dopamine D4 receptors, and briefly discuss their physiological and pathophysiological role in the brain.

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Section: Dopamine-related Diseasesmentioning

confidence: 96%

The dopamine D4 receptor: biochemical and signalling properties

Rondou

Haegeman

Craenenbroeck

2010

Cell. Mol. Life Sci.

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“…The TPH gene Chotai et al (2003) DSM-IV Italian 147 395 Serretti et al (2001) DSM-IV Italian 210 380 Paik et al (2000) DSM-III-R Korean 217 236 Hong et al (2001) DSM-IV Chinese 196 251 Sekizawa et al (2004) DSM-IV Japanese 51 148 Chao et al (2002) DSM-III-R African-American 41 17 Shinkai et al (2000) DSM-IV Japanese 182 148 The TH gene a Meloni et al (1995) DSM-III French Caucasian 94 145 DSM-III-R Tunisian 44 44 Wei et al (1995) C o n Wrmed by SAGB b United Kingdom 176 107 Jonsson et al (1996) DSM-III-R Caucasian 118 78 Burgert et al (1998) DSM the distribution of the alleles and genotypes among diVerent populations, such as the TH10 and TH9 alleles, suggesting that the polymorphism might be population-speciWc. It is noteworthy that for TH the Wrst published study reporting association of the genetic variant with schizophrenia may be a poor predictor of subsequent results (Table 1).…”

Section: Authormentioning

confidence: 99%

Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia

2006

Hum Genet

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A number of studies have suggested an association between schizophrenia and the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) genes. On the other hand, several studies attempting to replicate these findings have produced mixed results, possibly reflecting inadequate statistical power of the individual studies as well as the heterogeneity inherent in schizophrenia. In an attempt to clarify this inconsistency our meta-analysis has combined all the studies using multiple research methods published up to February 2006 to give a comprehensive picture of the role of three hydroxylase-related genes. The TPH A218C/A779C (OR = 1.18, 95% C.I. 1.06-1.33, P = 0.004) revealed a significant association with schizophrenia. However, the evidence for the TH and phenylalanine hydroxylase (PAH) genes was weak. No publication bias was detected in current studies. The findings, which may implicate the involvement of TPH in the pathogenesis of schizophrenia, have potentially important clinical, scientific and public health implications as well as providing a putative basis for the study of hydroxylase-related drugs. To our knowledge, this is the first meta-analysis of association between the three genes and schizophrenia.

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“…10 The 7R variant protein has functional properties distinct from other size variants in terms of clozapine binding 10 and effect on post-synaptic intracellular signal transduction. 11,12 Also, there has been growing literature reporting genetic association of the allele 7R with psychiatric traits/illnesses including novelty seeking, 13,14 attention-deficit hyperactivity disorder (ADHD) 15,16 as well as schizophrenia. 13,17 -31 Some studies declared association of the VNTR size polymorphisms with schizophrenia, 13,17,21,22,24,27 although not all studies agree.…”

Section: Introductionmentioning

confidence: 99%

Variable number of tandem repeat polymorphisms of DRD4: re-evaluation of selection hypothesis and analysis of association with schizophrenia

et al. 2008

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Associations have been reported between the variable number of tandem repeat (VNTR) polymorphisms in the exon 3 of dopamine D4 receptor gene gene and multiple psychiatric illnesses/traits. We examined the distribution of VNTR alleles of different length in a Japanese cohort and found that, as reported earlier, the size of allele '7R' was much rarer (0.5%) in Japanese than in Caucasian populations (B20%). This presents a challenge to an earlier proposed hypothesis that positive selection favoring the allele 7R has contributed to its high frequency. To further address the issue of selection, we carried out sequencing of the VNTR region not only from human but also from chimpanzee samples, and made inference on the ancestral repeat motif and haplotype by use of a phylogenetic analysis program. The most common 4R variant was considered to be the ancestral haplotype as earlier proposed. However, in a gene tree of VNTR constructed on the basis of this inferred ancestral haplotype, the allele 7R had five descendent haplotypes in relatively long lineage, where genetic drift can have major influence. We also tested this length polymorphism for association with schizophrenia, studying two Japanese sample sets (one with 570 cases and 570 controls, and the other with 124 pedigrees). No evidence of association between the allele 7R and schizophrenia was found in any of the two data sets. Collectively, this study suggests that the VNTR variation does not have an effect large enough to cause either selection or a detectable association with schizophrenia in a study of samples of moderate size.

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A search for association between schizophrenia and dopamine-related alleles

Cited by 47 publications

References 92 publications

The dopamine D4 receptor: biochemical and signalling properties

The dopamine D4 receptor: biochemical and signalling properties

Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia

Variable number of tandem repeat polymorphisms of DRD4: re-evaluation of selection hypothesis and analysis of association with schizophrenia

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