Association study of the SLC6A3 VNTR (DAT) and DRD2/ANKK1 Taq1A polymorphisms with alcohol dependence in a population from northeastern Brazil.

Background: Alcohol dependence (AD) is a complex psychiatric disorder, affecting 5.4% of the general population lifetime, characterized by excessive alcohol consumption influenced by environmental risk factors and genetic factors. Genetic alterations in dopaminergic system are involved in the treatment and etiology of AD.

Brugada syndrome in a family with a high mortality rate: a case report.

Introduction: Brugada syndrome is a hereditary arrhythmia characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death, with an apparent absence of structural abnormalities or ischemic heart disease. To date, mutations in the sodium channel, voltage-gated, type V, alpha subunit gene and glycerol-3-phosphate dehydrogenase 1-like gene are estimated to account for approximately 28% of Brugada syndrome probands.

Case Presentation: We report the case of a 32-year-old mixed-race Brazilian man who is sodium channel, voltage-gated, type V, alpha subunit gene and glycerol-3-phosphate dehydrogenase 1-like gene mutation-negative with a type 1 Brugada electrocardiographic pattern and a history of high family mortality, including five sudden deaths among relatives of whom four were first-degree relatives.

CYP3A5 and NAT2 gene polymorphisms: role in childhood acute lymphoblastic leukemia risk and treatment outcome.

Susceptibility to acute lymphoblastic leukemia can be highly influenced by genetic polymorphisms in metabolizing enzyme genes of environmental carcinogens. This study aimed to evaluate the impact of the CYP3A5 and NAT2 metabolizing enzyme polymorphisms on the risk of childhood acute lymphoblastic leukemia. The analysis was conducted on 204 ALL patients and in 364 controls from a Brazilian population, using PCR-RFLP.

Impact of thymidylate synthase promoter and DNA repair gene polymorphisms on susceptibility to childhood acute lymphoblastic leukemia.

The aim of this study was to evaluate the frequency of polymorphisms in the TYMS, XRCC1, and ERCC2 DNA repair genes in pediatric patients with acute lymphoblastic leukemia using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) approaches. The study was conducted in 206 patients and 364 controls from a Brazilian population. No significant differences were observed among the analyzed groups regarding XRCC1 codon 399 and codon 194 and ERCC2 codon 751 and codon 312 polymorphisms.

Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (NOS3) polymorphisms are associated with high relapse risk in childhood acute lymphoblastic leukemia (ALL).

Background: Angiogenesis has been shown as an important process in hematological malignancies. It consists in endothelial proliferation, migration, and tube formation following pro-angiogenic factors releasing, specially the vascular endothelial growth factor (VEGF), which angiogenic effect seems to be dependent on nitric oxide (NO). We examined the association among functional polymorphisms in these two angiogenesis related genes: VEGF (-2578C>A, -1154G>A, and -634G>C) and NOS3 (-786T>C, intron 4 b>a, and Glu298Asp) with prognosis of childhood acute lymphoblastic leukemia (ALL).

Frequency of polymorphisms and protein expression of cyclin-dependent kinase inhibitor 1A (CDKN1A) in central nervous system tumors.

Context And Objective: Genetic investigation of central nervous system (CNS) tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR) and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene in patients with and without CNS tumors.

Design And Setting: Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto.

Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute lymphoblastic leukemia in Brazilian children.

Polymorphic variations of several genes associated with dietary effects and exposure to environmental carcinogens may influence susceptibility to leukemia development. The objective of the present study was to evaluate the effect of the polymorphisms of debrisoquine hydroxylase (CYP2D6), epoxide hydrolase (EPHX1), myeloperoxidase (MPO), and quinone-oxoreductase (NQO1), which have been implicated in xenobiotic metabolism, on the risk of childhood acute lymphoblastic leukemia (ALL). We evaluated the frequency of polymorphisms in the CYP2D6 (*3 and *4), EPHX1 (*2 and *3), MPO (*2), and NQO1 (*2) genes in 206 patients with childhood ALL and in 364 healthy individuals matched for age and gender from a Brazilian population separated by ethnicity (European ancestry and African ancestry), using the PCR-RFLP method.

Polymorphisms in genes encoding drugs and xenobiotic metabolizing enzymes in a Brazilian population.

Polymorphic variations of several genes associated with drugs and xenobiotic metabolism have been linked to the factors that predispose to the carcinogenesis process. As considerable interindividual and interethnic variation in metabolizing enzyme activity has been associated with polymorphic alleles, we evaluated the frequency of the polymorphisms of CYP2D6, EPHX1 and NQO1 genes in 361 Brazilian individuals separated by ethnicity (European and African ancestry), using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The allele frequencies of the variants *3 and *4 for the gene CYP2D6 were 0.

Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia.

The interindividual variation in the activity of xenobiotic metabolizing enzymes and DNA repair genes could modify an individual's risk of recurrent malignancy and response to therapy. We investigated whether ALL outcome was related to polymorphisms in genes CYP2D6, MPO, EPHX1, NQO1, TS, XPD and XRCC1 in 95 consecutive ALL children by PCR or PCR-FRLP techniques. Polymorphisms in genes NQO1 and TS were associated with a significantly slow response to induction chemotherapy and NQO1 was also associated with a lower five-year event-free survival.

Polymorphisms in the thymidylate synthase promoter and the DNA repair genes XRCC1 and XPD in a Brazilian population.

Polymorphisms in genes responsible for maintaining genomic integrity are potential modifiers of disease risk. Since considerable interindividual and interethnic variation in DNA repair capacity has been associated with polymorphic alleles, we evaluated the frequency of the 2R/3R variants in the TS promoter, Arg194Trp and Arg399Gln in the XRCC1 gene, and Asp312Asn and Lys751Gln in the XPD gene in 364 healthy individuals from a Brazilian population separated by ethnicity (European ancestry and African ancestry). The genotypes were determined by PCR (TS) or by PCR-RFLP (XRCC1 and XPD).

Polymorphisms in glutathione S-transferases GSTM1, GSTT1 and GSTP1 and cytochromes P450 CYP2E1 and CYP1A1 and susceptibility to cirrhosis or pancreatitis in alcoholics.

Excessive alcohol consumption may cause the development of pathologies in the liver and pancreas and various digestive tract cancers. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1 and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, pesticides, environmental pollutants and alcoholic drinks. Polymorphisms in the genes coding for these enzymes have been associated with susceptibility to different diseases, including ethanol-related diseases.

Clastogenic effect of ethanol in chronic and abstinent alcoholics.

Alcoholism is one of the main causes of damage for human health, being relevant to study the induction of chromosomal aberrations (CA) by ethanol, and to investigate the individual susceptibility to diseases caused by alcoholism. A cytogenetic study was performed in human peripheral blood lymphocytes of 29 heavy chronic alcoholics, 11 alcoholics in abstinence, and 10 controls. The values of the chromosomal aberrations, mitotic indexes (MI) and proliferation indexes (PI) were determined.

Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1, and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, alcoholic drinks, pesticides, and environmental pollutants.