Estudio de variantes de los genes BDNF, COMT, DAT1 y SERT en niños colombianos con déficit de atención / Study of genetic variants in the BDNF, COMT, DAT1 and SERT genes in Colombian children with attention deficit disorder

Resumen Introducción: El trastorno por déficit de atención e hiperactividad (TDAH) es una perturbación con elevada prevalencia en población infantil de Bogotá. Entre las causas de este trastorno se encuentran factores genéticos y ambientales, pero pocos estudios han tratado de abordar el componente genético en población colombiana. Objetivos: Realizar un estudio de asociación genética entre diferentes polimorfismos y el TDAH en la población de Bogotá. Métodos: Múltiples polimorfismos de los genes DAT1, SERT, COMT y BDNF fueron genotipificados empleando las técnicas de PCR convencional y RFLP en 97 tríos de Bogotá. El test de desequilibrio de trasmisión (TDT) se empleó para determinar la asociación entre las diferentes variantes y el TDAH. Resultados: El análisis de TDT no identificó una transmisión preferencial de alelos de ninguna de las variantes estudiadas. Conclusiones: Nuestros resultados indican que la etiología del TDAH es heterogénea e involucra diversos factores genéticos. Futuros estudios enfocados en otros polimorfismos candidatos en una muestra más grande ayudarán a comprender el TDAH en la población colombiana.

Abstract Background: Attention deficit and hyperactive disorder (ADHD) is highly prevalent among children in Bogota City. Both genetic and environmental factors play a very important role in the etiology of ADHD. However, to date few studies have addressed the association of genetic variants and ADHD in the Colombian population. Objectives: To test the genetic association between polymorphisms in the DAT1, HTTLPR, COMT and BDNF genes and ADHD in a sample from Bogota City. Methods: We genotyped the most common polymorphisms in DAT1, SERT, COMT and BDNF genes associated with ADHD using conventional PCR followed by restriction fragment length polymorphism (RFLP) in 97 trios recruited in a medical center in Bogota. The transmission disequilibrium test (TDT) was used to determine the association between such genetic variants and ADHD. Results: The TDT analysis showed that no individual allele of any variant studied has a preferential transmission. Conclusions: Our results suggest that the etiology of the ADHD maybe complex and involves several genetic factors. Further studies in other candidate polymorphisms in a larger sample size will improve our knowledge of the ADHD in Colombian population.

Immunophenotypic markers in adult acute lymphoblastic leukemia: the prognostic significance of CD20 and TdT expression

BACKGROUND: Efforts to overcome poor outcomes in patients with adult acute lymphoblastic leukemia (ALL) have focused on combining new therapeutic agents targeting immunophenotypic markers (IPMs) with classical cytotoxic agents; therefore, it is important to evaluate the clinical significance of IPMs. METHODS: Baseline characteristics and clinical outcomes of patients with adult ALL were retrospectively analyzed. The percentage of blasts expressing IPMs at diagnosis was measured by multicolor flow cytometry analysis. Samples in which > or =20% of blasts expressed an IPM were considered positive. RESULTS: Among the total patient population (N=230), almost all (92%) were in first or second hematological complete remission (HCR) and 54% received allogeneic hematopoietic cell transplant (allo-HCT). Five-year hematologic relapse-free survival (HRFS) and overall survival (OS) rates were 36% and 39%, respectively, and 45.6% and 80.5% of patients were positive for the IPMs CD20 and terminal deoxynucleotidyl transferase (TdT), respectively. Expression of CD20, CD13, CD34, and TdT was associated with HRFS rate, and expression of CD20 and CD13 was associated with OS rate, as was the performance of allo-HCT. In multivariate analysis, positivity for CD20 (HRFS: hazard ratio [HR], 2.21, P<0.001; OS: HR, 1.63, P=0.015) and negativity for TdT (HRFS: HR, 2.30, P=0.001) were both significantly associated with outcomes. When patients were categorized into three subgroups according to positivity for CD20 and TdT, there were significant differences in HRFS and OS among the subgroups. CONCLUSION: Positivity for CD20 and TdT expression and clinical risk group were prognostic factors in adult ALL.

Examples and outlook of family-based cohort study / 한국역학회지

Family-based designs are commonly used in genetic association studies to identify and to locate genes that underlie complex diseases. In this paper, we review two examples of genome-wide association studies using family-based cohort studies, including the Framingham Heart Study and International Multi-Center ADHD Genetics Project. We also review statistical methods of family-based designs, including the transmission disequilibrium test (TDT), linkage analysis, and imprinting effect analysis. In addition, we evaluate the strengths and limitations of the family-based cohort design. Despite the costs and difficulties in carrying out this type of study, a family-based cohort study can play avery important role in genome wide studies. First, the design will be free from biases due to population heterogeneity or stratification. Moreover, family-based designs provide the opportunity to conduct joint tests of linkage and association. Finally, family-based designs also allow access to epigenetic phenomena like imprinting. The family-based cohort design should be given careful consideration in planning new studies for genome-wide strategies.

Family-Based Association Study of Tryptophan-2,3 Dioxygenase (TDO2) Gene and Autism Spectrum Disorder in the Korean Population

OBJECTIVES: Autism is a complex neurodevelopmental spectrum disorder with a strong genetic component. Previous neurochemical and genetic studies have suggested the possible involvement of the serotonin system in autism. Tryptophan 2,3-dioxygenase(TDO2) is the rate-limiting enzyme in the catabolism of tryptophan, which is the precursor of serotonin synthesis. The aim of this study was to investigate the association between the TDO2 gene and autism spectrum disorders(ASD) in a Korean population. METHODS: The patients were diagnosed with ASD on the basis of the DSM-IV diagnostic classification outlined in the Korean version of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The present study included the detection of four single nucleotide polymorphisms(SNPs) in the TDO2 gene(rs2292536, rs6856558, rs6830072, rs6830800) and the family-based association analysis of the single nucleotide polymorphisms in Korean ASD trios using a transmission disequilibrium test(TDT) and haplotype analysis. The family trios of 136 probands were included in analysis. 87.5% were male and 86.0% were diagnosed with autism. The mean age of the probands was 78.5+/-35.8 months(range: 26-264 months). RESULTS: Two SNPs showed no polymorphism, and there was no significant difference in transmission in the other two SNPs. We also could not find any significant transmission in the haplotype analysis(p>.05). CONCLUSION: We could not find any significant statistical association between the transmission of SNPs in the TDO2 gene and ASD in a Korean population. This result may not support the possible involvement of the TDO2 gene in the development of ASD, and further exploration might be needed to investigate other plausible SNP sites.

A Case of Acute Lymphoblastic Leukemia with Maturation / 대한혈액학회지

Acute lymphoblastic leukemia with maturation (ALLm) has different disease characteristics that does typical ALL. ALLm is characterized by an increased number of mature appearing leukemic cells (>20% of ANCs in the BM) having differentiation beyond the prolymphocyte stage according to light microscopic (LM) examination. It also has a worse prognosis than typical ALL. We have recently experienced a case of ALLm and we report on this case along with a literature review. A 36 year old patient showed lymphoblasts and mature appearing leukemic cells that were counted up to 15.8% and 23.0%, respectively, of the WBCs on bone marrow examination. Despite their mature appearance, these cells showed positivity for Tdt, CD10, CD19 and HLA-DR on the immunophenotypic study. Differentiating the mature-appearing leukemic cells from the hematogones or mature lymphocytes is difficult, and only through immunophenotypic examination is it possible to discriminate ALLm from typical ALL. We suggest performing a leukemic marker study that includes CD38 to effectively differentiate mature appearing leukemic cells from hematogones, especially for the follow up of leukemia with mature appearing cells.

Polymorphisms in Glutamate Receptor, Ionotropic, N-methyl-D-aspartate 2B(GRIN2B) Genes of Autism Spectrum Disorders in Korean Population: Family-based Association Study

OBJECTIVES: Autism is a complex neurodevelopmental spectrum disorder with a strong genetic component. Previous neurochemical and genetic studies suggested the possible involvement of glutamate N-methyl-D-aspartate(NMDA) receptor in autism. The aim of study was to investigate the association between the NMDA2B receptor gene(GRIN2B) and autism spectrum disorders(ASD) in the Korean population. METHODS: The patients with ASD were diagnosed with Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule based on DSM-IV diagnostic classification. The present study was conducted with the detection of four single nucleotide polymorphisms(SNPs) in GRIK2 and family-based association analysis of the single nucleotide polymorphisms in Korean ASD trios using transmission disequilibrium test (TDT). RESULTS: One hundred twenty six patients with ASD and their biological parents were analyzed. 86.5% were male and 85.1% were diagnosed as autistic disorder. The mean age was 71.9+/-31.6 months(range : 26-185 months). We found that rs1805247 showed significantly preferential transmission(TDT chi-square=12.8, p < 0.001) in ASD. CONCLUSION: One SNP in GRIN2B gene was significantly associated with ASD in the Korean population. This result suggests the possible involvement of glutamate NMDA receptor gene in the development of ASD.

Expression of death-associated protein kinase 1 in papillary thyroid carcinoma / 中国癌症杂志

Background and purpose: Death-associated protein kinase-1(DAPK) is a pro-apoptosis protein,and plays a important role in oncogenesis and development.This study is to investigate the expression of mRNA of DAPK1 and its association with apoptosis in papillary thyroid carcinoma(PTC).Methods:The expression of DAPK1 mRNA was detected by in situ hybridization in 45 cases of PTC and 45 cases of normal thyroid tissues next to tumors that consist of three part of tissue: normal thyroid tissue,nodular goiter and follicular adenoma.The apoptosis in corresponding issues was tested by TUNEL assay and the apoptosis index(AI) was evaluated.Results:The positive rate of DAPK1mRNA in PTC and para-PTC tissues were 37.78% and 71.11%,respectively.The positive rate of DAPK1 mRNA in counterpart thyroid issues was higher than that in tumor tissues(P0.05).Conclusions:As an apoptosis promoter,DAPK1 may function as an inhibitor of tumor,and low expression or loss DAPK1 gene may be involved in the oncogenesis of PTC.The detection of the expression of DAPK1 may be helpful for judging metastasis and prognosis of PTC.

T-lineage blast crisis of chronic myelogenous leukemia: simple record of 4 cases.

Blast crisis (BC) transformation in chronic myelogenous leukemia (CML) can involve each differentiation lineage of the hematopoietic system, i.e. granulocyte, monocyte, erythrocyte, megakaryocyte, and lymphocyte lineage. The lymphoid blast crisis (BC) leukemia cells usually belong to B-lineage, commonly having the phenotype of Pre-B stage of the B-lineage, in which cell-surface immunoglobulin (sIg) is not yet expressed. In contrast, T-lineage BC of CML is extremely rare. The objective of this study is to describe the fenotype, fusion transcript of bcr-abl, TdT, and cytoplasmic CD3 in T-lineage BC CML cases. Case report study. This report shows a simple summary of 4 cases of T-lineage BC of CML which have been collected in the phenotypic and genotypic analysis study for 17 years (1987-2004). In all cases, the chromosomal analysis revealed the presence of t(9;22)(q34;q11) at presentation. Cell surface analysis were done at diagnosis. Cases’ mononuclear cells stored as 10% DMSO were retrieved to be performed reverse transcription (RT) PCR BCR-ABL multiplex to demonstrate the presence of the fusion transcript of bcr-abl. RT-PCR was also performed for detecting the expression of cytoplasmic CD3ε and terminal deoxynucleotydil transferase (TdT). The results of cell surface antigen (CSA) at presentation showed that 1 case was CD7+, CD5-, and CD2-; 1 case CD7+, CD5+, and CD2-; and 2 cases CD7+, CD5+ and CD2+ indicating that all these T-lineage BC of CML cells show the phenotype of pre-(pro-) thymic stage phenotype. In the present study, two cases showed b2a2, one e1a2, and one negative bcr-abl transcript. The RT-PCR revealed the presence of CD3ε mRNA in all cases, and TdT mRNA in only one case. These results can constitute a basis for the future analysis of T-lineage BC of CML from now on.

A study about the apoptosis of epithelial cells in the fusing fetal rat palate / 대한치과교정학회지

The purpose of this study was to prove that the medial edge epithelial cells covering the secondary palatal shelves were removed by apoptosis during palatal fusion. 12 mature female rats (Suprague-Dawley) were mated overnight with male rats and sacrificed on days 16.0, 16.5, 16.75, 17.0 of pregnancy. The embryos were removed from the uterus and the heads were embedded in paraffin. The paraffin blocks were sectioned and the sections were undergone H-E staining for general histologic feature and TdT staining for detection of apoptotic cells. The obtained results were as follows. 1. In the section of 16.0 and 16.5 day embryos, the palatal shelves were prior to contact and no apoptotic cells wereobserved in the medial edge epithelium. At the initial contact of palatal shelves, there was a few apoptotic cells in the fusing epithelium. 2. In the 16.75 day embryos, the samples that epithelial seams did not lost there continuity, apoptotic cells were rarely seen at the midline epithelial seam. In contrast, a lot of apoptotic cells were observed at epithelial triangles and the junction between palatal shelves and nasal septum. 3. In the 16,75 day embryos, the samples that epithelial seams lost their continuity and disrupted to epithelial islands, large number, of apoptotic cells were observed at epithelial islands and epithelial triangles. Some apoptotic cells were also observed at the oral, nasal epithelium near the midline. 4. In the 17.0 day embryos, most of epithelial islands were disappeared and mesenchymal confluence was achieved. Apoptotic cells were rarely observed in the mesenchymal tissue which replaced epithelial islands, but there were some apoptotic cells at the epithelial triangles, oral and nasal epithelium. From the results of the study, it was revealed that medial edge epithelial cells of fusing palate were removed by apoptosis. Apoptotic cells were found mainly in the disappearing midline epithelial seam and the oral and nasal epithelial triangles at some late stages of palatal fusion.

Experimental study on the cardiomyocyte apoptosis in the early myocardial ischemia / 中国法医学杂志

In order to explore the significance of cardiomyocyte apoptosis in the early myocardial ischemia,the rat model of acute myocardial ischemia was established,and the apoptotic cells were detected in the early phase of ischemia(within 6h)with TUNEL method.The results showed that scanty apoptotic cells could be observed in the ischemic region 1h after ischemia,and reached the peak 3h after ischemia,then decreased.No apoptotic cells were found in the normal region.In the peri ischemic region,apoptotic cells could also be observed 1h after ischemia,and reached the peak 5h after ischemia.It is indicated that apoptosis is the major form of early ischemic myocardial damage,and the detection of apoptotic cardiomyocyte may provide a new sensitive and objective method for the postmortem diagnosis of early myocardial infarction.