RESUMO
BACKGROUND: The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence. METHODS: We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993. RESULTS: Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile. CONCLUSIONS: In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.
Assuntos
Alcoolismo/metabolismo , Etanol/farmacocinética , Adolescente , Adulto , Álcool Desidrogenase/genética , Alcoolismo/genética , Testes Respiratórios , Etanol/análise , Etanol/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Isoenzimas/genética , Masculino , Fatores de Risco , Fumar , GêmeosRESUMO
Drosophila larvae reared inside a micro-metal box with an internal field strength 0.004 microT, were treated with a magnetic field of 50 Hz, 8 microT. for 20 min. Control experienced 0.004 microT. Cellular transcript levels were assessed using slot blots and quantified using a Phosphorimager. Blots were hybridised using probes against HSP 70a, Histone 1.9, and Copia. The low frequency EMFs very significantly decreased transcript levels, indicating that experimental responses may be influenced by previous exposure or lack of previous exposure.
Assuntos
Campos Eletromagnéticos , Transcrição Gênica/efeitos da radiação , Análise de Variância , Animais , Sondas de DNA , Elementos de DNA Transponíveis/genética , Elementos de DNA Transponíveis/efeitos da radiação , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/efeitos da radiação , Histonas/genética , Histonas/efeitos da radiação , Processamento de Imagem Assistida por Computador , Immunoblotting , Proteínas de Insetos/genética , Proteínas de Insetos/efeitos da radiação , Larva/genética , Larva/efeitos da radiação , Modelos Lineares , Morfogênese/genética , Morfogênese/efeitos da radiação , Hibridização de Ácido NucleicoRESUMO
Previous studies found that MZ twin pairs who are blood group NN have greater intrapair variability in plasma lipid levels than those who are MM or MN. This led to the prediction that the response of plasma lipid levels to a low fat diet would depend on MN blood group, the greatest response being in those who are NN. The present study was based upon 254 patients who took part in the Australian Polyp Prevention Project. This was a 2 x 2 x 2 randomised factorial design based upon the presence or absence of the three factors: a dietary fibre supplement, a beta-carotene supplement and reduced intake of dietary fat. The lowering of plasma, low density lipoprotein (LDL) cholesterol, in response to a low fat diet was greatest in those who were NN and least in MN heterozygotes. Overall, a reduction in LDL level was observed in the 47% of the APPP population who were on a low fat diet and who were homozygous MM or NN. The result was consistent with a balanced polymorphism at or near the GLYA locus on chromosome 4 that influences the sensitivity of plasma lipid levels to dietary fluctuations in fat intake.