Association analysis between the C516T polymorphism in the 5-HT2A receptor gene and schizophrenia

Abstract

-Data from epidemiological studies have demonstrated that genetics is an important risk factor for schizophrenia. Disturbances of serotonergic brain pathways have been implicated in the pathophysiology of schizophrenia. Some studies have suggested that the efficacy of atypical antipsychotics on schizophrenia treatment may be related to the serotonin 2A receptor (5-HT2A), and that serotonergic drugs may induce psychotic symptoms. Thus, the aim of this study was to investigate the association between the C516T polymorphism and schizophrenia in a Brazilian population composed by 246 patients and 315 healthy matched controls in a case-control approach. No statistically differences were observed in allelic (χ 2 =1.77, 1d.f., p=0.18) or genotypic (χ 2 =1.69, 2d.f., p=0.42) distributions between cases and controls. The results suggest that the C516T polymorphism of the 5-HT2A receptor gene is not related to the susceptibility for schizophrenia in our Brazilian sample.KEY WORDS: serotonin, genetic association, allele, genotype, 5HT2A, schizophrenia. Análise de associação entre o polimorfismo C516T do gene do receptor 5-HT2A e esquizofreniaRESUMO -Estudos epidemiológicos têm demonstrado que o componente genético é importante fator de risco para o desenvolvimento de esquizofrenia. Alterações nas vias cerebrais serotonérgicas têm sido relacionadas à fisiopatologia da esquizofrenia. Algumas investigações têm sugerido que a eficácia de antipsicóticos atípicos no tratamento da esquizofrenia pode estar relacionada com sua ação no receptor de serotonina subtipo 2A (5-HT2A), e que drogas serotonérgicas podem provocar sintomas psicóticos. Assim, o objetivo desta investigação foi examinar a associação entre o polimorfismo C516T do gene do receptor 5-HT2A e esquizofrenia em uma amostra brasileira composta por 246 pacientes e 315 controles saudáveis e pareados em um estudo tipo caso-controle. Não foram observadas diferenças na distribuição alélica (χ 2 =1,77, 1d.f., p=0,18, 1d.f.) e genotípica (χ 2 =1,69, 2d.f., p=0,42) entre os grupos de pacientes e controles. Os resultados sugerem que o polimorfismo C516T gene do receptor 5-HT2A não é fator de susceptibilidade para esquizofrenia na amostra brasileira estudada.

A review of psychiatric genetics research in the Brazilian population

“…27 The same group (PROGENE) investigated polymorphisms from dopaminergic, noradrenergic and serotonergic genes (Ser-9-Gly DRD3 gene, VNTR DAT1 gene, 1287 A/G norepinephrine transporter/NET gene, G681C serotonin receptor/5-HT1Dbeta gene, C516T serotonin receptor/5-HT2A gene) and failed to find an association with SCZ. [28][29][30][31][32] In two studies, Oliveira et al addressed if a polymorphism in the promoter region of the SLC6A4 could be implicated in SCZ, BPD and dysthymia. 33,34 However, in both studies, there was no difference in alleles (long/short) neither in genotypes frequencies between any of the groups of patients and controls.…”

Study of association between genetic polymorphisms of phospholipase A2 enzymes and Alzheimer's disease

“…There are some reports showing association of homozygosity of other genetic polymorphisms and some neuropsychiatric disorders. This type of association may represent a heterozygosity advantage, probably because the presence of two different molecular forms of the neurotransmitter receptor, resulting in an increased ability to respond adaptively to variations in the environment 27 . However, in our sample there was not found such association as well.…”