Molecular-Ecogenetic study on the ethiology of alcoholism

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Alcoholism is multifactorial diseases influenced by gene-environmental interaction. Genetic variation of receptor may be associated with alcohol dependance due to its modified function in behavioral and physiological responces. In the present study, polymorphic alleles of cholecystokinin B receptor ( CCKBR), serotonin 1A receptor (HT1AR) , 00K gene and mt-DNA were analyzed. Different mutations were found in the exon of CCKBR and HT1AR.However genotypic distribution of alcoholics was not significantly different with that in controls. Analysis of the mt-DNA showed that a491 bp deletion in the sequence of ATPase exists as heteroplasmy in 58% of alcoholics but not in controls. The heteroplasmic deletion of mt-DNA may be a useful marker for alcohol abuse. Two nticleotide sequence variants were found in CCK gene ; a frequent mutation at nucleotide position -45 Cto T involved in core sequence of Spi binding cis-element of the promoter region, and a C to T substitution at 1662 position in intron 2. Patients with delirium tremens showed significantly higher frequency of the variant compared with the controls (x_24.91 p<0.03). Neuropeptide cholecystokinin (CCK) and the CCK receptors in central nervous system mediate actions on increasing firings, anxiety and nociceptions. These data suggested that the individuals possessing allelic mutation ( -45T ) in the promoter region of 00K gene might be susceptible to delirium tremens caused by alcohol abuse.