RESUMO
BACKGROUND: Fyn tyrosine kinase is a member of the Scr family that phosphorylates the NR2A and NR2B subunits of the NMDA receptors reducing the inhibitory effects of ethanol and therefore may regulate the individual sensitivity to ethanol. OBJECTIVES: To investigate whether there is any relationship between the polymorphism at position -93 of the Fyn kinase gene and the susceptibility to develop alcoholism. METHODS: We studied the distribution of genotypes and alleles of the polymorphism -93A/G (137346 T/C) in the 5' UTR region of the fyn gene in 207 male heavy drinkers (119 with alcohol dependence and 88 with alcohol abuse) and 100 control subjects from Castilla y León (Spain). RESULTS: The frequency of G allele carriers was higher in alcohol dependents than in alcohol abusers (47.9% vs 30.6%; p=0.015; OR=2.077; 95% CI 1.165-3.704). CONCLUSION: Our results show that the -93G allele of Fyn kinase gene is associated with higher risk to develop alcohol dependence in Spanish men.
Assuntos
Alcoolismo/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Proteínas Proto-Oncogênicas c-fyn/genética , População Branca/genética , Adulto , Idoso , Alcoolismo/metabolismo , Alelos , Mapeamento Cromossômico , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Espanha/etnologiaRESUMO
BACKGROUND: The tumor necrosis factor alpha gene (TNFA) has been recently associated to alcoholic steatohepatitis. We have analyzed the distribution of genotypes and alleles of two polymorphisms at positions -238 and -308 in the promoter region of the TNFA gene in a Spanish male population of alcoholics with and without alcoholic liver cirrhosis. METHODS: 149 male alcoholics (84 without alcoholic liver disease, and 65 with alcoholic liver cirrhosis) and 90 control subjects were included. Genotyping was done by polymerase chain reaction and digestion with restriction enzymes. RESULTS: No significant differences in the distribution of genotypes and alleles of the -308 TNFA gene polymorphism were observed between alcoholics and non-alcoholics, or between alcoholics with liver cirrhosis and those without liver disease. However, we found an association between the -238 TNFA polymorphism and alcoholic liver cirrhosis; the frequency of the heterozygous genotype being significantly higher in alcoholics with cirrhosis than in those without liver damage. CONCLUSION: The -238 TNFA-A allele is associated with a higher risk to develop alcoholic liver cirrhosis. This polymorphism could be considered as a genetic factors that confer predisposition to suffer liver cirrhosis in the alcoholic population of Castile and León.
