Pesquisa dos polimorfismos dos genes das enzimas álcool desidrogenase (ADH) e aldeído desidrogenase (ALDH) em mulheres etilistas, pacientes com distúrbios do espectro alcoólico fetal e grupo controle
Data
2013
Autores
Antonialli, Graziela Paronetto Machado 
Orientadores
Perez, Ana Beatriz Alvarez
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A dependencia do alcool e um importante problema de Saúde publica. O efeito teratogenico do alcool sobre o feto compreende um espectro de anomalias estruturais, neurologicas, cognitivas e comportamentais conhecidas como Desordens do Espectro Alcoolico Fetal u FASD. A influencia dos polimorfismos nos loci codificadores das enzimas alcool desidrogenase (ADH) e aldeido desidrogenase (ALDH) e bem caracterizada no risco do desenvolvimento da dependencia do alcool em algumas populacoes, e contribuiram para um melhor entendimento da contribuicao dos fatores geneticos na acao teratogenica do alcool. Objetivos: 1) Estudar as manifestacoes clinicas em amostra de pacientes com FASD; 2) Estabelecer a frequencia dos polimorfismos dos genes das enzimas ADH e ALDH em amostra de mulheres etilistas e grupo controle; 3) Estabelecer a frequencia dos polimorfismos estudados nos pacientes com FASD; 4) Estabelecer a correlacao entre os genotipos encontrados nos pacientes com FASD, mulheres etilistas e grupo controle e sua repercussao na prole. Metodos: 1) Os pacientes com diagnostico de FASD foram avaliados pelos Criterios Diagnosticos de Washington; 2) As Mulheres etilistas foram avaliadas por instrumentos de rastreamento do uso inadequado do alcool; 3) O DNA genomico foi isolado de sangue periferico para deteccao dos polimorfismos dos genes das enzimas ADH e ALDH por PCR e eletroforese em gel; 4) Os resultados foram analisados estatisticamente. Resultados: As distribuicoes genotipicas dos polimorfismos das enzimas ADH1B, ADH1C e ALDH2 no Grupo Controle foram semelhantes as descritas para algumas populacoes brancas de europeus e americanos, e diferentes das frequencias descritas em asiaticos e africanos. O alelo ADH1B*3 (Arg369Cys) foi significativamente mais frequente entre os pacientes com FASD quando comparado com o grupo controle (p<0,0001), sugerindo que este alelo pode conferir risco para o desenvolvimento dos fenotipos da FASD. O alelo ADH1C*2 (Ile349Val) foi significativamente menos frequente entre as etilistas (p=0,0058) e os pacientes com FASD (p=0,0157) quando comparado com o grupo controle, sugerindo que este alelo pode conferir protecao tanto contra o desenvolvimento do etilismo quanto contra o desenvolvimento dos fenotipos da FASD.
Introduction: Alcohol dependence is a major social and economic problem worldwide. The teratogenicity of alcohol comprises a spectrum of anomalies known as Fetal Alcohol Spectrum Disorders - FASD. The influence of the polymorphisms in the code regions of the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzyme is well characterized as a risk factor for alcohol dependence in some populations, and contributed to a better understanding of the genetic factors in the teratogenic action of alcohol. Purpose: 1) To Study clinical sample in patients with FASD; 2) To determine the frequency of ADH and ALDH polymorphism enzymes in Brazilian alcohol abusers woman and control group; 3) To determine the frequency of these polymorphisms in a sample of patients with FASD; 4) To Establish the correlation between genotypes in patients with FASD, alcohol abusers woman and control group, and its repercussions in the offspring. Methods: 1) Patients with FASD were evaluated according to the Washington Criteria Diagnosis; 2) Alcohol abusers woman were screened by instruments for alcohol misuse; 3) DNA was isolated from peripheral blood, amplified by PCR reaction, digested by specific restriction enzyme and analyzed by gel electrophoresis. Results: The genotype distribution of the ADH1B, ADH1C and ALDH2 enzyme polymorphism found in our control group were similar to those previously described in white European and American, but quite different from the frequency described in Asian. The ADH1B*3 allele (Arg369Cys) was significantly more frequent in FASD patients (p<0,001) compared to the healthy Brazilian population. The ADH1C*2 allele (Ile349Val) was significantly less frequent in FASD patients (p=0,0057) and alcohol abuser (p=0,0058) when compared to the healthy Brazilian population. Conclusion: Although it is still a small sample, we can conclude that the ADH1B*3 allele may be a risk factor to the Fetal Alcohol Spectrum and the ADH1C*2 allele can act as a protective factor to alcohol dependence in women and hence to to the Fetal Alcohol Spectrum in the Brazilian population.
Introduction: Alcohol dependence is a major social and economic problem worldwide. The teratogenicity of alcohol comprises a spectrum of anomalies known as Fetal Alcohol Spectrum Disorders - FASD. The influence of the polymorphisms in the code regions of the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzyme is well characterized as a risk factor for alcohol dependence in some populations, and contributed to a better understanding of the genetic factors in the teratogenic action of alcohol. Purpose: 1) To Study clinical sample in patients with FASD; 2) To determine the frequency of ADH and ALDH polymorphism enzymes in Brazilian alcohol abusers woman and control group; 3) To determine the frequency of these polymorphisms in a sample of patients with FASD; 4) To Establish the correlation between genotypes in patients with FASD, alcohol abusers woman and control group, and its repercussions in the offspring. Methods: 1) Patients with FASD were evaluated according to the Washington Criteria Diagnosis; 2) Alcohol abusers woman were screened by instruments for alcohol misuse; 3) DNA was isolated from peripheral blood, amplified by PCR reaction, digested by specific restriction enzyme and analyzed by gel electrophoresis. Results: The genotype distribution of the ADH1B, ADH1C and ALDH2 enzyme polymorphism found in our control group were similar to those previously described in white European and American, but quite different from the frequency described in Asian. The ADH1B*3 allele (Arg369Cys) was significantly more frequent in FASD patients (p<0,001) compared to the healthy Brazilian population. The ADH1C*2 allele (Ile349Val) was significantly less frequent in FASD patients (p=0,0057) and alcohol abuser (p=0,0058) when compared to the healthy Brazilian population. Conclusion: Although it is still a small sample, we can conclude that the ADH1B*3 allele may be a risk factor to the Fetal Alcohol Spectrum and the ADH1C*2 allele can act as a protective factor to alcohol dependence in women and hence to to the Fetal Alcohol Spectrum in the Brazilian population.
Descrição
Citação
ANTONIALLI, Graziela Paronetto Machado. Pesquisa dos polimorfismos dos genes das enzimas álcool desidrogenase (ADH) e aldeído desidrogenase (ALDH) em mulheres etilistas, pacientes com distúrbios do espectro alcoólico fetal e grupo controle. 2013. 145 f. Dissertação (Mestrado em Biologia Estrutural e Funcional) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2013.