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1.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 42(2): 128-135, Mar.-Apr. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1089246

RESUMO

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Citalopram/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Estimulação Transcraniana por Corrente Contínua , Catecol O-Metiltransferase/genética , Método Duplo-Cego , Resultado do Tratamento , Terapia Combinada , Fator Neurotrófico Derivado do Encéfalo/genética , Polimorfismo de Nucleotídeo Único , Receptor 5-HT2A de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Oxigenases de Função Mista/genética , Pessoa de Meia-Idade , Antidepressivos/uso terapêutico
2.
Rev. bras. psiquiatr ; 39(4): 302-308, Oct.-Dec. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-899370

RESUMO

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.


Assuntos
Humanos , Masculino , Feminino , Adulto , Esquizofrenia/genética , Catecol O-Metiltransferase/genética , Córtex Pré-Frontal/metabolismo , Memória de Curto Prazo/fisiologia , Fenótipo , Esquizofrenia/fisiopatologia , Esquizofrenia/metabolismo , Haplótipos , Catecol O-Metiltransferase/metabolismo , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Frequência do Gene , Genótipo , Testes Neuropsicológicos
3.
Yonsei Medical Journal ; : 721-727, 2016.
Artigo em Inglês | WPRIM | ID: wpr-21841

RESUMO

PURPOSE: Alexithymia, defined as a deficit in the ability to recognize and describe one's own feelings, may be related to the development and maintenance of obsessive-compulsive symptoms. The aim of this study was to evaluate the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and alexithymia in patients with obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: We recruited 244 patients with OCD (169 males, 75 females). Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20), and genotyping of the COMT Val(158)Met polymorphism was evaluated. RESULTS: Patients with the COMT Val/Val genotype had significantly higher total and "difficulty identifying feelings" (DIF) subdimension scores than those with the Val/Met or Met/Met genotypes. Patients with the COMT Val/Val genotype had significantly higher "difficulty describing feelings" (DDF) subdimension scores than those with the COMT Val/Met genotype. However, there were no differences in the scores for the "externally oriented thinking" (EOT) subdimension among the three genotypes. CONCLUSION: These results indicate that the high-activity Val allele of the COMT Val(158)Met polymorphism is associated with increased alexithymic traits in patients with OCD. The present finding suggests that alexithymia is an endophenotype of OCD that is mediated by the COMT Val(158)Met polymorphism.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sintomas Afetivos/diagnóstico , Alelos , Catecol O-Metiltransferase/genética , Genótipo , Transtorno Obsessivo-Compulsivo/diagnóstico , Fenótipo , Polimorfismo Genético , República da Coreia
4.
Journal of Korean Medical Science ; : 757-763, 2016.
Artigo em Inglês | WPRIM | ID: wpr-11693

RESUMO

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Etários , Alelos , Estudos de Casos e Controles , Catecol O-Metiltransferase/genética , Genótipo , Transtorno de Pânico/genética , Polimorfismo de Nucleotídeo Único , Qualidade de Vida , Análise de Regressão , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Fatores Sexuais
5.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 37(3): 235-241, July-Sept. 2015. tab, ilus
Artigo em Inglês | LILACS | ID: lil-759435

RESUMO

Objective:To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.Methods:Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance.Results:For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001).Conclusion:Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Catecol O-Metiltransferase/genética , Cognição/fisiologia , Epistasia Genética , Polimorfismo de Nucleotídeo Único , /genética , Esquizofrenia/genética , Análise de Variância , Estudos de Casos e Controles , Escolaridade , Função Executiva/fisiologia , Frequência do Gene , Estudos de Associação Genética , Testes Neuropsicológicos , Reação em Cadeia da Polimerase em Tempo Real , Esquizofrenia/fisiopatologia
6.
Journal of Forensic Medicine ; (6): 197-201, 2014.
Artigo em Chinês | WPRIM | ID: wpr-983907

RESUMO

The prevalence of violence behavior in patients with schizophrenia is higher than that in common population. Data suggest that genetic factors may play a substantial role for the etiology of the behavior. Among the particular gene polymorphisms that have been considered to be involved in violence behavior, the catechol-O-methyltransferase (COMT) gene had been the focus of recent research. This article reviews the association research between COMT gene and violence behavior in patients with schizophrenia in several aspects: SNP polymorphism of COMT Val158Met and COMT Ala72Ser, haplotype of COMT gene and DNA methylation of promoter region of COMT gene. The genetic research direction is presented for patients with schizophrenia.


Assuntos
Humanos , Agressão , Catecol O-Metiltransferase/genética , Haplótipos , Polimorfismo Genético , Esquizofrenia/genética , Violência
7.
Indian J Biochem Biophys ; 2013 Oct; 50(5): 436-441
Artigo em Inglês | IMSEAR | ID: sea-150253

RESUMO

In view of documented evidence demonstrating the association of dopaminergic metabolism and neurotransmission with Parkinson’s disease (PD), a case-control study was conducted to investigate the impact of particular polymorphisms in the catechol O-methyl transferase (COMT) H108L, monoamine oxidase B (MAOB) int 13 A>G, dopamine transporter 1 (DAT1) A1215G, dopamine receptor D2 (DRD2) Taq1A, DRD2 Taq1B and DRD2 Taq1D genes on the susceptibility to PD. PCR-RFLP method was used for the genetic analysis. The COMT H108L polymorphism increased PD risk by 1.4-fold (95%CI: 1.02-1.98), whereas reduced risk was observed with MAOB int 13 A>G polymorphism (OR: 0.77, 95%CI: 0.51-0.99). Multifactor dimensionality reduction analysis showed gene-gene interactions between these two loci that resulted in loss of the protective role of MAOB G-allele in the presence of COMT L-allele. DAT1A1215G polymorphism in the exon 9 was not associated with PD. Individually, DRD2 polymorphisms showed null association. However, all-variant haplotype of DRD2 locus i.e. T-G-T haplotype showed 29.8-fold risk for PD compared to all-wild haplotype i.e., C-A-C haplotype (95%CI: 6.85-130.4). To conclude, genetic variants of COMT, MAOB and DRD2 loci modulate susceptibility to PD in South Indian subjects.


Assuntos
Catecol O-Metiltransferase/genética , Feminino , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Monoaminoxidase/genética , Doença de Parkinson/enzimologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2/genética
8.
Indian J Hum Genet ; 2013 Oct-Dec ;19 (4): 408-411
Artigo em Inglês | IMSEAR | ID: sea-156605

RESUMO

OBJECTIVES: Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol‑O‑methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma. MATERIALS AND METHODS: In this study, 34 cases with prostate carcinoma whose first‑degree relatives had prostate carcinoma and 30 healthy age‑matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction‑restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age‑matched male controls were enrolled to analyze the genotype of these two genes. RESULTS: Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 × baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk. CONCLUSION: Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low‑penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.


Assuntos
Catecol O-Metiltransferase/genética , Receptor alfa de Estrogênio/genética , Família/história , Predisposição Genética para Doença/genética , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Turquia/epidemiologia
9.
Journal of Korean Medical Science ; : 1403-1406, 2013.
Artigo em Inglês | WPRIM | ID: wpr-44040

RESUMO

This study evaluated the family-based genetic association between autism spectrum disorders (ASDs) and 5 single-nucleotide polymorphisms (SNPs) in the catechol-o-methyltransferase gene (COMT), which was found among 151 Korean ASDs family trios (dominant model Z = 2.598, P = 0.009, P(FDR) = 0.045). We found a statistically significant allele transmission or association in terms of the rs6269 SNP in the ASDs trios. Moreover, in the haplotype analysis, the haplotypes with rs6269 demonstrated significant evidence of an association with ASDs (additive model rs6269-rs4818-rs4680-rs769224 haplotype P = 0.004, P(FDR) = 0.040). Thus, an association may exist between the variants of the COMT gene and the occurrence of ASDs in Koreans.


Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Masculino , Alelos , Povo Asiático/genética , Catecol O-Metiltransferase/genética , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Genótipo , Haplótipos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , República da Coreia
10.
Rev. chil. neuropsicol. (En línea) ; 7(3): 115-121, dic. 2012. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-722452

RESUMO

El nivel de Dopamina en la Corteza Prefrontal se ha relacionado al desempeño de las Funciones Ejecutivas (FE). El objetivo de este estudio es explorar el efecto del polimorfismo funcional del gen COMT (Val/Val,Val/Met y Met/Met) en las FE de preescolares. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas para niños, y se extrajo el ADN genómico según metodología estándar (N=248) de 3 a 6 años de edad (M=4.6). Se estudiaron las frecuencias genotípicas del gen COMT y se realizó un análisis de varianza (ANOVA one-way) estableciendo diferencias significativas con una p<0.05. Los niños con el polimorfismo de baja actividad Met/Met puntúan significativamente mejor en relación a los niños con polimorfismo Val/Val en pruebas que requieren de Inhibición y los niños con el polimorfismo de alta actividad Val/Val resultan con un mejor rendimiento en pruebas relacionadas a MT, Planeación y Abstracción que los niños con polimorfismo Met/Met y Val/Met. Estos resultados parecen reflejar el papel de la enzima COMT como regulador de DA y que tanto el hipermetabolismo como el hipometabolismo tiene implicaciones importantes en las FE.


The level of DA in the prefrontal cortex has been related to the performance on executive functions (EF). The objective of this study was to explore the effect of the COMT polymorphism (Val/Val, Val/Met, Met/Met) in the performance of EF in a population of preschool children. All subjects were evaluated with a Neuropsychological Battery and genomic DNA was extracted according to standard methodology (N=248) from 3 to 6 years of age (M=4.6). We studied genotypic frequencies of the COMT gene and an analysis of variance (one-way ANOVA) with post hoc analysis, establishing significant differences at p<0.05. In Children with a low activity polymorphism Met/Met scored significantly better in relation to the children with polymorphism Val/Val in tests requiring inhibition and children with high activity polymorphism Val/Val had better performance on tests related to working memory, planning and abstraction that children with polymorphism Met/Met and Val/Met. These results seem to reflect the role of COMT enzyme as a regulator of DA and that both hypermetabolism and hypometabolism has important implications for the EF.


Assuntos
Feminino , Pré-Escolar , Criança , Catecol O-Metiltransferase/genética , Dopamina/genética , Função Executiva/fisiologia , Polimorfismo Genético , Análise de Variância , Estudos Transversais , Genótipo , Metionina/genética , Valina/genética
11.
Arq. neuropsiquiatr ; 70(12): 913-916, Dec. 2012. tab
Artigo em Inglês | LILACS | ID: lil-660312

RESUMO

Schizophrenia is a severe psychiatric disorder with frequent recurrent psychotic relapses and progressive functional impairment. It results from a poorly understood gene-environment interaction. The gene encoding catechol-O-methyltransferase (COMT) is a likely candidate for schizophrenia. Its rs165599 (A/G) polymorphism has been shown to be associated with alteration of COMT gene expression. Therefore, the present study aimed to investigate a possible association between schizophrenia and this polymorphism. The distribution of the alleles and genotypes of this polymorphism was investigated in a Brazilian sample of 245 patients and 834 controls. The genotypic frequencies were in Hardy-Weinberg equilibrium and no statistically significant differences were found between cases and controls when analyzed according to gender or schizophrenia subtypes. There was also no difference in homozygosis between cases and controls. Thus, in the sample studied, there was no evidence of any association between schizophrenia and rs165599 (A/G) polymorphism in the non-coding region 3' of the COMT gene.


A esquizofrenia é um grave transtorno psiquiátrico que apresenta freqüentes recorrências psicóticas e incapacitação progressiva. Resulta de uma interação gene-ambiente ainda pouco compreendida. O gene da catecol-O-metiltransferase (COMT) é considerado um possível candidato para esquizofrenia. O polimorfismo genético rs165599 (A/G) da COMT foi associado com alteração da expressão do seu gene. Assim, o presente trabalho tem como objetivo investigar a possível associação de tal polimorfismo com esquizofrenia. A distribuição de seus alelos e genótipos foi investigada em uma amostra brasileira composta de 245 pacientes e 834 controles. As frequências genotípicas estavam em equilíbrio de Hardy-Weinberg e não se encontrou diferença estatisticamente significante entre casos e controles, quando analisados por gênero e subtipos da esquizofrenia. Não houve também diferença de homozigosidade entre casos e controles. Desse modo, na amostra estudada, não houve evidência de associação entre esquizofrenia e o polimorfismo rs165599 (A/G) localizado na região 3' não codificadora do gene da COMT.


Assuntos
Feminino , Humanos , Masculino , Catecol O-Metiltransferase/genética , Predisposição Genética para Doença , Frequência do Gene/genética , Polimorfismo Genético/genética , Esquizofrenia/enzimologia , Esquizofrenia/genética , Estudos de Casos e Controles , Genótipo
12.
Journal of Forensic Medicine ; (6): 299-304, 2012.
Artigo em Chinês | WPRIM | ID: wpr-983753

RESUMO

Catechol-O-methyltransferase (COMT) gene encodes catechol-O-methyltransferase, the variant of this gene may affect the expression and metabolic activity of COMT. As the result of the changes of the effective concentration of the catecholamine neurotransmitter in the central nervous system, central nervous system dysfunctions associated with schizophrenia. This review summarizes genetic polymorphism and diversity of COMT gene. It also elaborates the relation between SNP and haplotype of COMT gene and three aspects, which including schizophrenia, attacking and violent tendency, and the frontal cognitive function of the schizophreniac. The correlativity study between genetic variation of the COMT gene and schizophrenia in patients with attacking and violent tendency may be helpful for the assessment of forensic psychiatry.


Assuntos
Humanos , Agressão/psicologia , Encéfalo/patologia , Catecol O-Metiltransferase/genética , Cognição/fisiologia , Dopamina/metabolismo , Genética Forense , Expressão Gênica , Predisposição Genética para Doença , Variação Genética , Genótipo , Haplótipos , Reação em Cadeia da Polimerase , Polimorfismo Genético , Córtex Pré-Frontal/patologia , Regiões Promotoras Genéticas , Esquizofrenia/genética , Violência/psicologia
13.
Indian J Biochem Biophys ; 2011 Aug; 48(4): 283-289
Artigo em Inglês | IMSEAR | ID: sea-135330

RESUMO

The present study was aimed to investigate the modulatory role of plasma folate and eight putatively functional polymorphisms of one-carbon metabolism on catecholamine methyltransferase (COMT)-mediated oxidative DNA damage and breast cancer risk. Plasma folate and 8-oxo-2’-deoxyguanosine (8-oxodG) were estimated by commercially available kits, while polymorphisms were screened by PCR-RFLP and PCR-AFLP methods. COMT H108L polymorphism showed independent association with breast cancer (OR: 1.73, 95% CI: 1.31-2.30). No significant interaction was observed between folate status and COMT genotype. Multifactor dimensionality reduction (MDR) analysis gave evidence for the significant epistatic (gene-gene) interactions (p<0.0001) of COMT H108L with reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5’-UTR 3R2R, TYMS 3’-UTR ins6/del6. Increased plasma 8-oxodG were observed in cases compared to controls (mean ± SE: 5.59 ± 0.60 vs. 3.50 ± 0.40 ng/ml, p<0.004). Plasma folate deficiency alone was not a significant predictor of 8-oxodG elevation. The genotype combinations namely, RFC1 G80A/methionine synthase reductase (MTRR) A66G, RFC1 G80A/SHMT C1420T/TYMS 3R2R and serine hydroxymethyltransferase (SHMT) C1420T/TYMS 3R2R/methionine synthase (MTR) A2756G/COMT H108L were strong predictors of 8-oxodG elevation in the order of risk. To conclude, the current study provides substantial evidence for a cross talk between one-carbon metabolism and COMT catalysis that might influence oxidative DNA damage and breast cancer risk.


Assuntos
Sequência de Bases , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Estudos de Casos e Controles , Catecol O-Metiltransferase/genética , Dano ao DNA , Primers do DNA , Feminino , Ácido Fólico/sangue , Humanos , Oxirredução , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição
14.
Journal of Korean Medical Science ; : 701-710, 2011.
Artigo em Inglês | WPRIM | ID: wpr-188474

RESUMO

Panic disorder is one of the chronic and disabling anxiety disorders. There has been evidence for either genetic heterogeneity or complex inheritance, with environmental factor interactions and multiple single genes, in panic disorder's etiology. Linkage studies have implicated several chromosomal regions, but no research has replicated evidence for major genes involved in panic disorder. Researchers have suggested several neurotransmitter systems are related to panic disorder. However, to date no candidate gene association studies have established specific loci. Recently, researchers have emphasized genome-wide association studies. Results of two genome-wide association studies on panic disorder failed to show significant associations. Evidence exists for differences regarding gender and ethnicity in panic disorder. Increasing evidence suggests genes underlying panic disorder overlap, transcending current diagnostic boundaries. In addition, an anxious temperament and anxiety-related personality traits may represent intermediate phenotypes that predispose to panic disorder. Future research should focus on broad phenotypes, defined by comorbidity or intermediate phenotypes. Genome-wide association studies in large samples, studies of gene-gene and gene-environment interactions, and pharmacogenetic studies are needed.


Assuntos
Humanos , Catecol O-Metiltransferase/genética , Colecistocinina/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Monoaminoxidase/genética , Transtorno de Pânico/genética
15.
Rev. bras. reumatol ; 50(2): 141-149, mar.-abr. 2010. tab, ilus
Artigo em Inglês, Português | LILACS | ID: lil-552814

RESUMO

INTRODUÇÃO: A fibromialgia é uma síndrome reumática caracterizada por dor difusa e crônica associada a fadiga, insônia, ansiedade, depressão, perda de memória e tontura. Embora os mecanismos fisiológicos que controlam a fibromialgia não tenham sido estabelecidos, fatores neuroendócrinos, genéticos ou moleculares podem estar envolvidos. OBJETIVO: O objetivo do presente estudo foi caracterizar os polimorfismos dos genes do receptor de serotonina (5-HT2A) e da catecolO-metiltransferase (COMT) em pacientes brasileiros com fibromialgia, a fim de avaliar sua participação na etiologia da doença. MATERIAL E MÉTODOS: O DNA genômico extraído de 102 amostras de sangue (51 pacientes, 51 controles) foi usado para a caracterização molecular dos polimorfismos dos genes 5-HT2A e COMT, por meio de PCR-RFLP. RESULTADOS: A análise molecular dos polimorfismos do gene 5-HT2A demonstrou frequências de 25,49 por cento C/C, 49,02 por cento T/C e 25,49 por cento T/T, nos pacientes com fibromialgia, e 17,65 por cento C/C, 62,74 por cento T/C e 19,61 por cento T/T, no grupo controle, não apresentando diferença significativa entre o grupo de pacientes e o grupo controle. Os polimorfismos do gene da COMT em pacientes com fibromialgia apresentaram uma frequência de 17,65 por cento e 45,10 por cento para os genótipos H/H e L/H, respectivamente. No grupo controle, as frequências foram de 29,42 por cento, para H/H, e 60,78 por cento, para L/H, sem diferença significativa entre ambos os grupos. Entretanto, houve diferença significativa na frequência do genótipo L/L em pacientes (37,25 por cento) e controles (9,8 por cento), o que permitiu a diferenciação entre os dois grupos. CONCLUSÃO: A frequência do genótipo L/L foi maior nos pacientes com fibromialgia. Apesar de a fibromialgia envolver uma situação poligênica e fatores ambientais, o estudo molecular do SNP rs4680 do gene da COMT pode auxiliar a identificação de indivíduos suscetíveis.


INTRODUCTION: Fibromyalgia is a rheumatic syndrome characterized by diffuse and chronic pain associated with fatigue, sleep disorders, anxiety, depression, memory loss, and dizziness. Although the physiological mechanisms that control fibromyalgia have not been precisely established, neuroendocrine, genetic or molecular factors may be involved in fibromyalgia. OBJECTIVE: The aim of the present study was to characterize serotonin receptor (5-HT2A) and catecholO-methyltransferase (COMT) gene polymorphisms in Brazilian patients with fibromyalgia and to evaluate the participation of these polymorphisms in the etiology of the disease. MATERIAL AND METHODS: Genomic DNA extracted from 102 blood samples (51 patients, 51 controls) was used for molecular characterization of the 5-HT2A and COMT gene polymorphisms by PCR-RFLP. RESULTS: Analysis of the 5-HT2A polymorphism revealed a frequency of 25.49 percent C/C, 49.02 percent T/C and 25.49 percent T/T in patients, and of 17.65 percent C/C, 62.74 percent T/C and 19.61 percent T/T in the control group, with no differences between the two groups.Analysis of the COMT polymorphism in patients showed a frequency of 17.65 percent and 45.10 percent for genotypes H/H and L/H, respectively. In the control group the frequency was 29.42 percent for H/H and 60.78 percent for L/H, also with no differences between the two groups. However, there was a significant difference in the frequency of the L/L genotype between patients (37.25 percent) and controls (9.8 percent), which permitted differentiation between the two groups. CONCLUSION: The L/L genotype was more frequent among fibromyalgia patients. Though considering a polygenic situation and environmental factors, the molecular study of the rs4680 SNP of the COMT gene may be helpful to the identification of susceptible individuals.


Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Catecol O-Metiltransferase/genética , Fibromialgia/genética , Polimorfismo Genético , /genética , Fibromialgia/etiologia , Inquéritos e Questionários
16.
J Genet ; 2002 Aug; 81(2): 65-71
Artigo em Inglês | IMSEAR | ID: sea-114253

RESUMO

Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A number of candidate genes, a majority of them from the monoaminergic pathway in the brain, have been very popular in association studies with schizophrenia, a neuropsychiatric disorder. In this study diallelic/multiallelic polymorphisms in some dopaminergic, serotonergic and membrane-phospholipid-related genes have been evaluated in a control population recruited from North India. Association, if any, of these allelic variants with schizophrenia has been tested using a case-control approach. The case data have been taken from our published family-based association studies in schizophrenia. Of the eight genes tested in this study, association with schizophrenia was observed for only two gene polymorphisms, one in the promoter region of the serotonin 2A receptor gene and the other in the tryptophan hydroxylase gene. One new allele for the dopamine transporter gene (with eight repeats, 570-bp size), not reported in any population so far, has been identified in one individual in our sample. The data generated in this study, besides providing a normative background for various disease association studies, are a significant contribution to the population-specific genome database, a currently growing requirement.


Assuntos
Adulto , Estudos de Casos e Controles , Catecol O-Metiltransferase/genética , Dopamina/metabolismo , Feminino , Frequência do Gene , Humanos , Índia , Masculino , Fosfolipases A/genética , Monoéster Fosfórico Hidrolases/genética , Polimorfismo Genético , Receptores de Serotonina/genética , Esquizofrenia/genética , Triptofano Hidroxilase/genética
17.
J Biosci ; 2002 Feb; 27(1 Suppl 1): 35-52
Artigo em Inglês | IMSEAR | ID: sea-110752

RESUMO

Schizophrenia is a severe neuropsychiatric disorder with a polygenic mode of inheritance which is also governed by non-genetic factors. Candidate genes identified on the basis of biochemical and pharmacological evidence are being tested for linkage and association studies. Neurotransmitters, especially dopamine and serotonin have been widely implicated in its etiology. Genome scan of all human chromosomes with closely spaced polymorphic markers is being used for linkage studies. The completion and availability of the first draft of Human Genome Sequence has provided a treasure-trove that can be utilized to gain insight into the so far inaccessible regions of the human genome. Significant technological advances for identification of single nucleo-tide polymorphisms (SNPs) and use of microarrays have further strengthened research methodologies for genetic analysis of complex traits. In this review, we summarize the evolution of schizophrenia genetics from the past to the present, current trends and future direction of research.


Assuntos
Antecipação Genética , Catecol O-Metiltransferase/genética , Cromossomos Humanos/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina , Genoma Humano , História do Século XX , Humanos , Índia , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras/genética , Biologia Molecular , Monoaminoxidase/genética , Proteínas do Tecido Nervoso , Polimorfismo de Nucleotídeo Único/genética , Receptores Dopaminérgicos/genética , Receptores de Serotonina/genética , Esquizofrenia/genética , Tirosina 3-Mono-Oxigenase/genética
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