Genetic polymorphisms of SNP loci in the 5' and 3' region of TPH2 gene in Northern Chinese Han population / 法医学杂志

OBJECTIVE@#To investigate the genetic polymorphism in the 5' and 3' region of TPH2 gene of Northern Chinese Han population and to explore its application value in forensic medicine.@*METHODS@#The sequence variants and the genetic polymorphisms of 6 SNP loci (rs4570625, rs11178997, rs11178998, rs41317118, rs17110747 and rs41317114) within a 905 bp 5' flanking region and a 1,104bp 3' flanking region of TPH2 gene were analyzed by DNA sequencing in a total of 244 unrelated healthy individuals in Northern Chinese Han population. The statistical analysis was carried out by Haploview v4.2 software.@*RESULTS@#The genotypic distributions of the 6 SNP loci in the TPH2 gene were in accordance with Hardy-Weinberg equilibrium. One C/T variant in 92922 site was found. There was a high linkage disequilibrium among the 3 SNP loci (rs4570625, rs11178997 and rs11178998) in the 5' region and the 3 SNP loci (rs41317118, rs17110747 and rs41317114) in the 3' region of TPH2 gene, respectively. The parameters of population genetics of 6 SNP loci were obtained.@*CONCLUSION@#There are great polymorphisms in the 5' and 3' region of TPH2 gene in Northern Chinese Han population, which could be used as genetic indexes for association analysis of the related diseases, as well as for forensic individual identification and paternity testing.

Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder / Associação entre polimorfismos do gene da triptofano hidroxilase 2 e o transtorno obsessivo-compulsivo

OBJECTIVE: A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis, is considered an important candidate gene associated with psychiatric disorders. METHOD: Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview®. RESULTS: Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION: Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.

OBJETIVO: Diversos estudos demonstram que o transtorno obsessivo-compulsivo apresenta considerável contribuição genética, com diversos genes candidatos tendo sido estudados por meio de estudos de associação. Como alterações do sistema serotonérgico estão associadas ao transtorno obsessivo-compulsivo, o gene da triptofano hidroxilase 2, enzima limitante da síntese da serotonina, é plausível candidato para estudos. MÉTODO: Nossa amostra é composta de 321 sujeitos (107 pacientes com transtorno obsessivo-compulsivo e 214 controles) e investigamos oito tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 e rs10879357) do gene da triptofano hidroxilase 2. Análise estatística foi realizada com os programas UNPHASED e Haploview. RESULTADOS: Análise de frequência alélica e genotípica entre casos e controles não evidenciaram diferenças estatisticamente significativas. No entanto, observamos maior prevalência dos haplótipos T-C-T (rs4448731, rs4565946, rs10506645) e C-A-T (rs4565946, rs7955501, rs10506645) entre os pacientes, assim como duas regiões com importantes desequilíbrios de ligação (SNPs rs4448731 e rs4565946; SNPs rs10506645 e 4760820). DISCUSSÃO: Nossos achados não demonstraram uma associação entre os SNPs do gene da TPH2 e o transtorno obsessivo-compulsivo, porém mais estudos são necessários, já que fortes desequilíbrios de ligação foram demonstrados, assim como dois haplótipos.

No Evidence of an Association between A218C Polymorphism of the Tryptophan Hydroxylase 1 Gene and Aggression in Schizophrenia in a Korean Population

PURPOSE: We investigated the association between the tryptohan hydroxylase 1 (TPH1) gene and aggression in schizophrenia in a Korean population. MATERIALS AND METHODS: The sample included 61 aggressive patients as well as 104 non-aggressive patients from psychiatric hospitals and 335 healthy volunteers in Korea. Blood samples were collected from all participants for TPH1 A218C genotyping. The patients were administered standard psychiatric interviews as well as a self-report questionnaire for anger-related traits. RESULTS: In the case-control phenotypic comparisons, there was no significant association between the aggressive patients and the TPH1 A218C polymorphism. There was no significant effect of the TPH1 genotype on the anger-related traits, or no significant interaction between the genotype and group (aggressive and non-aggressive patients). CONCLUSION: These findings suggest that TPH1 does not play a major role in aggressive behavior via anger in schizophrenic patients.

Polymorphism of TPH gene T3792A locus in Han ethnic group of north China / 法医学杂志

OBJECTIVE@#To investigate the polymorphism of the TPH gene T3792A locus in Han ethnic group of north China and its application value in forensic science.@*METHODS@#The polymorphism of T3792A locus of the TPH gene was analyzed by the ASPCR of blood samples from 173 unrelated individuals of north Chinese Han population.@*RESULTS@#The distribution of the T3792A locus polymorphism of the TPH gene in Han ethnic group of north China followed the Hardy-Weinberg law, with the allele A and T gene frequency of 0.486 and 0.514, respectively.@*CONCLUSION@#The TPH gene T3792A locus shows a very good genetic polymorphism, and may be applied to individual identification and paternity testing.

Distribution of tryptophan hydroxylase gene-T457C locus polymorphism in Han ethnic group in northern China / 法医学杂志

OBJECTIVE@#To study the distribution of the tryptophan hydroxylase (TPH) gene-T457C locus polymorphism in Han ethnic group in northern China and to find its applicable value in forensic science.@*METHODS@#Genomic DNA samples, extracted from 180 unrelated individuals in northern Chinese Han population, were analyzed by PCR-RFLP.@*RESULTS@#The discrimination power (DP) value and the power of exclusion (PE) value of the TPH gene-T457C locus were 0.624 and 0.187, respectively. The allele frequency showed significant difference from that of French people (P=0.04).@*CONCLUSION@#Polymorphism of the TPH gene-T457C locus could show ethnic and regional differences. It has a potential to be used in forensic science.

Candidate gene polymorphisms among North Indians and their association with schizophrenia in a case-control study.

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.

Elevación de la fracción libre de L-triptófano plasmático en lactantes desnutridos in utero hasta el tercer mes de edad postnatal / Increased levels of free plasma L-trypthophan in nursing infants with malnutrition in utero up to the third month of extra-uterine life

Introducción. Se ha demostrado en la rata que la desnutrición adquirida durante la gestación y en la lactancia produce elevación del L-Triptófano (L-Trp) tisular y de la actividad de la triptófano-5-hidroxilasa (TrpOH), que da como resultado una aceleración de la síntesis de 5-hidroxitriptamina (5-HT, serotonina). Este cambio metabólico parece también cumplirse en los recién nacidos humanos desnutridos in utero, en cuyo plasma aumenta la fracción libre del L-Trp y disminuye el unido a albúmina, lo que sugiere que hay más L-Trp disponible para pasar al cerebro humano y aumentar la síntesis del neurotransmisor. El objetivo del presente estudio fue demostrar que la fracción libre de L-Trp plasmático, está aumentada hasta el tercer mes de edad en los lactantes desnutridos in utero. Material y métodos. Se realizó un estudio prospectivo longitudinal y comparativo, con el seguimiento de 2 grupos de recién nacidos pretérmino de 33 a 36 semanas de edad gestacional; un grupo de 11 niños desnutridos y el otro de 14 niños sanos; durante los primeros 3 meses de vida en los que se determinó la fracción libre y la unida a albúmina de L-Trp, así como la 5-HT y la albúmina en el plasma. Los resultados fueron comparados con la prueba de anova de dos vías para mediciones repetidas y el coeficiente de Pearson; con un nivel de significancia de P menor de 0.05. Resultados. En los lactantes desnutridos, al nacimiento, al primero, segundo y tercer mes de edad se observó: a) elevación de la fracción libre del L-Trp; b) la fracción unida o albúmina del aminoácido y la albúmina en el plasma fueron significativamente menores en comparación a sus controles de la misma edad y c) la concentración de 5-HT plásmatica mostró disminución significativa en los desnutridos a partir del segundo mes de edad. Conclusiones. Los resultados de este estudio confirman que la fracción libre del L-Trp está significativamente elevada en los lactantes desnutridos in utero durante los primeros tres meses de vida. El aumento de L-Trp en el plasma sugiere que el transporte del aminoácido al cerebro está aumentado y que hay activación en la síntesis de serotonina cerebral. Por lo anterior se ha propuesto en la síntesis de serotonina cerebral. Por lo anterior se ha propuesto en este estudio a la fracción libre de L-Trp plasmático como un indicador indirecto de la alteración en la síntesis de serotonina cerebral en este tipo de pacientes