Association between the DRD2-141C Insertion/Deletion polymorphism and schizophrenia

Abstract

-Epidemiological studies have demonstrated that the genetic component is an important risk factor for the development of schizophrenia. The genes that codify the different compounds of the dopaminergic system have created interest for molecular investigations in patients with schizophrenia because the antipsychotic drugs, especially those of first generation, act on this cerebral system. Thus the aim of the present study was to investigate the possible association between the -141 Ins/Del (rs1799732) polymorphism of the dopamine receptor type 2 (DRD2) and schizophrenia. The distribution of the alleles and genotypes of the studied polymorphism was investigated in a sample of 229 patients and 733 controls. There were statistical differences in the allelic (c 2 =9.78; p=0.001) and genotypic genotypic (c 2 =12.74; p=0.001) distributions between patients and controls. Thus the -141C Ins/Del polymorphism of the DRD2 gene (allele Ins) was associated to the SCZ phenotype in the investigated sample.KEY WORDS: dopamine, genetics, D2, receptor, schizophrenia.Associação entre o polimorfismo -141c ins/Del do gene do DRD2 e esquizofrenia resumo -Estudos epidemiológicos têm demonstrado que o componente genético é um importante fator de risco para o desenvolvimento de esquizofrenia. Os genes que codificam os diferentes componentes do sistema dopaminérgico passaram a despertar interesse para os estudos moleculares em pacientes com esquizofrenia, devido ao fato dos antipsicóticos, em especial os de primeira geração, exercerem sua ação nesse sistema. Assim, o objetivo do presente estudo foi investigar a possível associação entre polimorfismo -141C Ins/Del (rs1799732) do gene do receptor dopaminérgico tipo 2 (DRD2) e esquizofrenia. Um total de 229 pacientes e 733 controles pareados para sexo e idade foi selecionado com o objetivo de investigar a distribuição dos alelos e genótipos do polimorfismo investigado entre os grupos de pacientes e controles. Houve diferença estatisticamente significante nas distribuições alélica (c 2 =9,78; p=0,001) e genotípica (c 2 =12,74; p=0,001) entre pacientes e controles. Assim, o polimorfismo -141C Ins/Del do gene do DRD2 (alelo Ins) está associado à esquizofrenia na amostra estudada.

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

“…The − 141 C Ins/Del deletion variant is associated with reduced D2 receptor gene expression in transfected cells, and post-mortem data suggested reduced D2 receptor binding in carriers of the deletion variant (Arinami et al, 1997). The − 141 C Ins/Del insertion variant has been found to be associated with schizophrenia in independent Japanese (Arinami et al, 1997;Ohara et al, 1998), Swedish (Jonsson et al, 1999b) and Spanish populations (Cordeiro et al, 2009;Lafuente et al, 2008). However, this finding could not be replicated in other studies (Parsons et al, 2007;Stober et al, 1998;Tallerico et al, 1999), and one study in a British population found a reverse association, with the − 141 C deletion variant being more frequent in patients with schizophrenia than in controls (Breen et al, 1999).…”

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

“…After reviewing the full text, 15 studies were excluded as six were reviews [18,19,[29][30][31][32], two were in Russian [33,34], one was in Polish [35], one was based on family members [36], two observed HWE disequilibrium in the control group [37,38] and three had overlapping data [39][40][41]. Thus, a total of 31 articles [8,[11][12][13][14][15][16]20,21, were included in this metaanalysis. The detailed retrieval process is shown in Figure 1.…”

“…Several studies have shown that the Taq1A polymorphism of DRD2 increases susceptibility to schizophrenia [11,12], but other papers have shown contrary results [13,14]. The -141C Ins/Del (rs1799732) polymorphism of DRD2 has also been reported to be involved in schizophrenia risk [15,16], but again results have been inconsistent.…”

Association study between the rs165599 catechol-O-methyltransferase genetic polymorphism and schizophrenia in a Brazilian sample

“…Therefore, the genes involved in the dopaminergic system are potential targets for genetic association investigations in schizophrenia. Polymorphisms in dopamine transporter and receptors genes have been widely investigated as risk factors for schizophrenia development, but the results have been inconclusive [2][3][4][5] . Thus, other possible candidates for such investigations are the enzymes that metabolize dopamine, such as catechol-O-methyltransferase (COMT).…”