INVESTIGATION OF GENETIC RISK-FACTORS ASSOCIATED WITH ALCOHOLISM

Alcoholism is a multifactorial disease influenced by genetic-environme ntal interaction. Genetic variation of the receptor may be associated with alcohol dependence due to its modified function in behavioral and physiological responses. In the present study, polymorphic alleles of cholecystokinin B receptor (CCKBR), serotonin 1A receptor (HT1AR) gen es, and mitochondrial DNA were analyzed. DNAs were isolated from the b lood samples of 112 healthy controls and 106 alcoholics. Genetic varia tion was detected by SSCP analysis, followed by direct sequencing of p olymerase chain reaction product as well as restriction fragment-lengt h polymorphism. Three different mutations were found in the exon 3 seq uence of CCKBR: His (CAT) at aa207 --> His (CAC) (5.4%), Arg (CGC) at aa215 --> His (CAC) (4.5%), and Val (GTG) at aa138 --> Met (ATG) (0.9% ) in controls. Genotypic distribution of alcoholics was not significan tly different with that in controls. A proline (CCG) to leucine (CTG) substitution at amino acid 16 of HT1AR was found in alcoholics (4.5%) and in controls (4.7%). This mutation site of HT1AR was different in c omparison with the variants reported by Nakhai et al. (Biochem Biophys . Res. Commun. 210:530-536, 1995). Analysis of the mitochondrial DNA s howed that a 491 bp deletion in the sequence of ATPase exists as heter oplasmy in 58% of alcoholics, but not in controls. Heteroplasmic delet ion of mitochondrial DNA may be a useful marker for alcohol abuse. Fur ther study is undergoing to elucidate the cause and significance of th is deletion in alcoholics.