ABSTRACT
Serotonergic system dysfunction has been implicated in the etiology of suicide. A large number of genetic studies have focused on the potential involvement of genes coding for components of serotonergic system in suicidal behavior. However, other genes belonging to this system remain to be investigated or have been poorly studied, as is the case of the 5-HT6 receptor (5-HTR6) gene. In this study, we investigated the potential association between the 5-HTR6 gene 267C/T SNP and suicide in a Portuguese population. Blood samples were collected from 179 suicide victims and 189 controls. Genotypes for the 5-HTR6 gene 267C/T SNP were obtained with the restriction enzyme Rsa I. A tendency was found for genotype association between this polymorphism and suicide, but the differences were not statistically significant (chi(2)=5.374, df=2, p=0.068). However, a gender-specific association was detected when comparing the genotype distribution between male suicide victims and male controls (chi(2)=6.988, df=2, p=0.030), suggesting that this SNP might have a role in the etiology of suicide in male subjects in the Portuguese population.
Subject(s)
Receptors, Serotonin/genetics , Suicide , Adolescent , Adult , Aged , Aged, 80 and over , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Portugal , Sex Factors , Young AdultABSTRACT
BACKGROUND: Alterations of the gamma-aminobutyric acid (GABA) system have been implicated in the pathophysiology of major psychoses. OBJECTIVE: Restriction fragment length polymorphisms associated with the human gamma-aminobutyric acid type A (GABAA) beta2 and GABAA gamma2 subunit genes on chromosome 5q32-q35 were tested to determine whether they confer susceptibility to major psychoses. METHODS: Thirty-two schizophrenic families and 25 bipolar families were tested for linkage. RESULTS: Nonparametric linkage (NPL) analysis performed by GENEHUNTER showed no significant NPL scores for both genes in schizophrenia (GABAA beta2: NPL narrow= -0.450; NPL broad= -0.808; GABAA gamma2: NPL narrow=0.177; NPL broad= -0.051) or bipolar disorder (GABAA beta2: NPL narrow=0.834; NPL broad=0.783; GABAA gamma2: NPL narrow= -0.159; NPL broad=0.070). CONCLUSION: Linkage analysis does not support the hypothesis that variants within the GABAA beta2 and GABAA gamma2 genes are significantly linked to major psychoses in a Portuguese population.
Subject(s)
Genetic Linkage/genetics , Protein Subunits/genetics , Psychotic Disorders/genetics , Receptors, GABA-B/genetics , Bipolar Disorder/genetics , Bipolar Disorder/metabolism , Humans , Introns/genetics , Phenotype , Polymerase Chain Reaction , Polymorphism, Genetic/genetics , Population Surveillance/methods , Prefrontal Cortex/metabolism , Protein Subunits/metabolism , Psychotic Disorders/metabolism , Receptors, GABA-A/metabolism , Receptors, GABA-B/metabolism , Schizophrenia/genetics , Schizophrenia/metabolismABSTRACT
Genetic factors play a major role in the etiology of schizophrenia and disturbances of serotonergic pathways have been implicated in this disorder. The aim of the present study was to examine genetic association between schizophrenia and polymorphisms in the 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) autoreceptor genes in ninety trios from Portugal. No association or linkage disequilibrium was obtained between schizophrenia and 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT). Concerning 5-HT1Dbeta autoreceptor gene, also negative results was obtained in the analysis of the haplotypes with transmit. Thus, our data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population.
Subject(s)
Linkage Disequilibrium , Polymorphism, Single Nucleotide , Receptor, Serotonin, 5-HT1B/genetics , Receptor, Serotonin, 5-HT1D/genetics , Schizophrenia/genetics , Autoreceptors/genetics , Family Health , Genetic Predisposition to Disease , Haplotypes , Humans , Molecular Epidemiology , Portugal/epidemiology , Risk , Schizophrenia/epidemiology , Schizophrenia/etiologyABSTRACT
BACKGROUND: Alterations in dopaminergic and serotonergic systems have been implicated in the pathophysiology of schizophrenia for many years. This study was performed to assess the possible involvement of the dopamine receptor genes D2 (DRD2), D3, D4, serotonin receptor genes 1Da, 1Db, and 2A in the etiology of schizophrenia. METHODS: We examined 33 multiplex schizophrenic families from Portugal. RESULTS: Linkage analysis performed by GENEHUNTER showed nonsignificant linkage for these genes. A maximum nonparametric linkage score of 1.635 (P=.032) at DRD2 gene was observed, and this finding suggests DRD2 gene for further studies. CONCLUSION: the polymorphisms studied at dopamine receptor genes D3, D4, serotonin receptor genes 1Da, 1Db, and 2A do not have a major effect in susceptibility to schizophrenia in a Portuguese population.
Subject(s)
Dopamine/genetics , Genetic Linkage/genetics , Schizophrenia/epidemiology , Schizophrenia/genetics , Serotonin/genetics , Chromosomes, Human, Pair 13/genetics , DNA Mutational Analysis , Humans , Point Mutation/genetics , Statistics, NonparametricABSTRACT
Schizophrenia is a highly heritable condition, as demonstrated in family, twin and adoption studies. Candidate genes from the dopaminergic system have long been hypothesized to be involved in the etiology of this disorder. In the present study, we investigated the genetic association between polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3) genes and schizophrenia. We examined 90 trios from Portugal, and negative results were obtained from association studies with both Haplotype Relative Risk (HRR) and Transmission Disequilibrium Test (TDT), as well as TRANSMIT. Therefore, we conclude that neither the DRD2 nor the DRD3 gene polymorphisms investigated are associated with schizophrenia in our sample.
Subject(s)
Gene Expression/genetics , Polymorphism, Genetic/genetics , Receptors, Dopamine D2/genetics , Schizophrenia/genetics , Catchment Area, Health , Diagnostic and Statistical Manual of Mental Disorders , Female , Haplotypes/genetics , Humans , Male , Portugal/epidemiology , Receptors, Dopamine D3 , Schizophrenia/diagnosisABSTRACT
Alterations in dopaminergic system have been implicated in the pathophysiology of this disease for many years, and this study was performed to assess the possible involvement of the dopamine D4 receptor (DRD4) gene polymorphisms either in the 5' upstream or in the coding regions, in the etiology of schizophrenia. The approach included an association study with 90 Portuguese trios by doing the analysis of the individual alleles and the haplotypes. For the polymorphisms in the 5' upstream region (-C616G and -C521T) and in the coding region (48 bp repeat) of the DRD4 gene, negative results were obtained with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT), as well as transmit. These data suggest that polymorphisms (-C616G, -C521T, and 48 bp repeat) at the DRD4 gene do not have a minor effect in the susceptibility to schizophrenia in our sample.
