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.
Assuntos
Alcoolismo/genética , Cirrose Hepática Alcoólica/genética , Polimorfismo Genético/genética , Fator de Necrose Tumoral alfa/genética , População Branca/genética , Adulto , Idoso , Alcoolismo/etnologia , Triagem de Portadores Genéticos , Predisposição Genética para Doença/genética , Testes Genéticos , Genótipo , Humanos , Cirrose Hepática Alcoólica/etnologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Espanha/etnologiaRESUMO
AIMS: In an attempt to explain differences in susceptibility to alcoholism and alcohol liver disease (ALD), different genes have been analysed, among them those encoding inflammatory cytokines. Thus, it has been reported recently that both the interleukin 1 receptor antagonist (IL1RN) and the IL1beta (IL1B) genes may influence the risk of ALD in Japanese alcoholics. We analysed the distribution of single nucleotide polymorphisms (SNPs) located in the IL1A, IL1B, IL1R1 and IL1RN genes in alcoholic and non-alcoholic Spanish subjects. METHODS: DNA samples were obtained from 139 male alcoholics, 78 of whom were diagnosed as alcohol dependent (32 patients with liver cirrhosis and 46 without ALD) and 61 as alcohol abusers (25 with liver cirrhosis and 36 without ALD). As a control, we studied 81 age- and sex-matched healthy volunteers. RESULTS: Alleles -511 IL1B*1 and IL1RN*1 were represented more in alcoholic patients than in the control group. We did not find any association of alcoholism or ALD with polymorphisms in the IL1A and IL1R1 genes. CONCLUSIONS: We conclude that the proteins encoded by the IL1RN and IL1B genes may be involved in susceptibility to alcoholism in Spanish men, probably through a different pathway from that involved in the regulation of the inflammatory response.