Investigação genético-molecular do tipo caso-controle em uma amostra de mulheres portadoras de psicose funcional do primeiro estudo de alto-risco brasileiro

OBJECTIVE: Data from epidemiological studies have demonstrated that genetics is an important risk factor for psychosis. The present study is part of a larger project, pioneer in Brazil, which has been conducted by other researchers who intend to follow a high-risk population (children) for the development of schizophrenia and bipolar disorder. In this first phase of the project, the objective was to investigate the distribution of four candidate genetic polymorphisms for functional psychosis (Ser9Gly DRD3, 5HTTLPR, the VNTR 3'-UTR SLC6A3 and Val66Met BDNF) in a case-control sample. METHOD: A total of 105 women (58 with schizophrenia and 47 with bipolar disorder) and 62 gender-matched controls were investigated. RESULTS: Allele and genotype distributions of all identified functional polymorphisms did not differ statistically between cases and controls. CONCLUSIONS: These results suggest that the investigated polymorphisms were not related to susceptibility to functional psychoses in our Brazilian sample. These findings need to be validated in larger and independent studies.OBJETIVO: Estudos epidemiológicos demonstram que alterações genéticas são fatores de risco importantes para o desenvolvimento de psicose. O presente estudo é parte um projeto maior, pioneiro no Brasil, realizado com mais pesquisadores, que pretende seguir uma população de alto risco genético para o desenvolvimento de esquizofrenia e transtorno bipolar. Nesta primeira fase, o objetivo foi investigar a distribuição de quatro polimorfismos genéticos candidatos no desenvolvimento de psicose funcional (Ser9Gly DRD3, 5HTTLPR, o VNTR 3'-UTR SLC6A3 e Val66Met BDNF) em uma amostra caso-controle. MÉTODO: O estudo genético respeitou o desenho metodológico do estudo clínico. Um total de 105 mulheres (58 esquizofrenia e 47 transtorno bipolar) e 62 controles sem diagnóstico psiquiátrico foi investigado. RESULTADOS: Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos investigados. CONCLUSÕES: Os resultados sugerem que estes polimorfismos não estavam relacionados à suscetibilidade para psicose funcional nesta amostra brasileira estudada. Esses achados precisam ser validados em estudos maiores e independentes

Investigation of possible association between Ser9Gly polymorphism of the D3 dopaminergic receptor gene and response to typical antipsychotics in patients with schizophrenia

Typical antipsychotics have a high affinity for dopamine receptors. It is therefore of interest to investigate such loci in pharmacogenetic studies on psychosis. We investigated the hypothesis that Ser9Gly polymorphism of the DRD3 gene may play a role in the differences in individual response to typical antipsychotics between schizophrenic patients. The sample was composed of 53 good responders and 59 poor ones. No significant differences between the good and poor responders were found in the allelic distribution (good responders: Ser9 61.32%, Gly9 38.67%; poor responders: Ser9 64.40%, Gly9 35.59%; odds ratio, OR = 0.88, 0.49 < OR < 1.56; chi2 = 0.23, 1 degree of freedom, df, p = 0.63) and genotype distribution (good responders: Ser9/Ser9 37.73%, Ser9/Gly9 47.16%, Gly9/Gly9 15.09%; poor responders: Ser9/Ser9 42.37%, Ser9/Gly9 44.06%, Gly9/Gly9 13.55%; chi2 = 0.25, 2 df, p = 0.88). Nor was there any association with homozygosity (good responders: homozygous: 52.82%, heterozygous: 47.16%; poor responders: homozygous: 55.92%, heterozygous: 44.06%; odds ratio, OR = 0.88, 0.39 < OR < 1.99; chi2 = 0.11, 1 df, p = 0.74). The results did not support the hypothesis that Ser9Gly polymorphism of the DRD3 gene influences the response to typical antipsychotics in our sample of schizophrenics

Association analysis between the C516T polymorphism in the 5-HT2A receptor gene and schizophrenia Análise de associação entre o polimorfismo C516T do gene do receptor 5-HT2A e esquizofrenia

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 (chi2=1.77, 1d.f., p=0.18) or genotypic (chi2=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.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 (chi2=1,77, 1d.f., p=0,18, 1d.f.) e genotípica (chi2=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

Molecular genetic case-control women investigation from the first Brazilian high-risk study on functional psychosis Investigação genético-molecular do tipo caso-controle em uma amostra de mulheres portadoras de psicose funcional do primeiro estudo de alto-risco brasileiro

OBJECTIVE: Data from epidemiological studies have demonstrated that genetics is an important risk factor for psychosis. The present study is part of a larger project, pioneer in Brazil, which has been conducted by other researchers who intend to follow a high-risk population (children) for the development of schizophrenia and bipolar disorder. In this first phase of the project, the objective was to investigate the distribution of four candidate genetic polymorphisms for functional psychosis (Ser9Gly DRD3, 5HTTLPR, the VNTR 3'-UTR SLC6A3 and Val66Met BDNF) in a case-control sample. METHOD: A total of 105 women (58 with schizophrenia and 47 with bipolar disorder) and 62 gender-matched controls were investigated. RESULTS: Allele and genotype distributions of all identified functional polymorphisms did not differ statistically between cases and controls. CONCLUSIONS: These results suggest that the investigated polymorphisms were not related to susceptibility to functional psychoses in our Brazilian sample. These findings need to be validated in larger and independent studies.OBJETIVO: Estudos epidemiológicos demonstram que alterações genéticas são fatores de risco importantes para o desenvolvimento de psicose. O presente estudo é parte um projeto maior, pioneiro no Brasil, realizado com mais pesquisadores, que pretende seguir uma população de alto risco genético para o desenvolvimento de esquizofrenia e transtorno bipolar. Nesta primeira fase, o objetivo foi investigar a distribuição de quatro polimorfismos genéticos candidatos no desenvolvimento de psicose funcional (Ser9Gly DRD3, 5HTTLPR, o VNTR 3'-UTR SLC6A3 e Val66Met BDNF) em uma amostra caso-controle. MÉTODO: O estudo genético respeitou o desenho metodológico do estudo clínico. Um total de 105 mulheres (58 esquizofrenia e 47 transtorno bipolar) e 62 controles sem diagnóstico psiquiátrico foi investigado. RESULTADOS: Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos investigados. CONCLUSÕES: Os resultados sugerem que estes polimorfismos não estavam relacionados à suscetibilidade para psicose funcional nesta amostra brasileira estudada. Esses achados precisam ser validados em estudos maiores e independentes

Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer

A detailed genome mapping analysis of 213,636 expressed sequence tags (EST) derived from nontumor and tumor tissues of the oral cavity, larynx, pharynx, and thyroid was done. Transcripts matching known human genes were identified; potential new splice variants were flagged and subjected to manual curation, pointing to 788 putatively new alternative splicing isoforms, the majority (75%) being insertion events. A subset of 34 new splicing isoforms (5% of 788 events) was selected and 23 (68%) were confirmed by reverse transcription-PCR and DNA sequencing. Putative new genes were revealed, including six transcripts mapped to well-studied chromosomes such as 22, as well as transcripts that mapped to 253 intergenic regions. in addition, 2,251 noncoding intronic RNAs, eventually involved in transcriptional regulation, were found. A set of 250 candidate markers for loss of heterozygosis or gene amplification was selected by identifying transcripts that mapped to genomic regions previously known to be frequently amplified or deleted in head, neck, and thyroid tumors. Three of these markers were evaluated by quantitative reverse transcription-PCR in an independent set of individual samples. Along with detailed clinical data about tumor origin, the information reported here is now publicly available on a dedicated Web site as a resource for further biological investigation. This first in silico reconstruction of the head, neck, and thyroid transcriptomes points to a wealth of new candidate markers that can be used for future studies on the molecular basis of these tumors. Similar analysis is warranted for a number of other tumors for which large EST data sets are available.Univ São Paulo, Fac Med, Inst Psiquiatria, Neurosci Lab,Dept Psiquiatria, BR-05403010 São Paulo, BrazilUniv São Paulo, Fac Med, Dept Bioquim, BR-05403010 São Paulo, BrazilUniv São Paulo, Fac Med, Lab Bioinformat, Inst Quim, BR-05403010 São Paulo, BrazilUniv São Paulo, Fac Med, Disciplina Oncol, Dept Radiol, BR-05403010 São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Dept Med & Morfol, São Paulo, BrazilHosp Canc AC Camargo, Dept Cirurg Cabeca & Pescoco & Otorrinolaringolog, São Paulo, SP, BrazilUniv Estadual Campinas, Inst Biol, Dept Genet & Evolucao, Lab Biol Mol & Genom Hemoctr, Campinas, SP, BrazilUniv Estadual Campinas, Inst Biol, Dept Genet & Evolucao, Lab Genom & Expressao, Campinas, SP, BrazilUniv Estadual Paulista, Dept Biol, Inst Biociencias, Araraquara, SP, BrazilFac Med Sao Jose Rio Preto, Dept Biol Mol, Sao Jose de Rio Preto, SP, BrazilUniv Estadual Paulista, Escola Farm, Dept Ciencias Biol, Araraquara, SP, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Dept Med & Morfol, São Paulo, BrazilWeb of Scienc