Genetic determinants of alcohol addiction and metabolism: A survey in Italy

Background: Although multiple genes are involved in alcoholism and can cont ribute differently to the risk of dependence and liver damage, no studies h ave investigated susceptibility to addiction in combination with susceptibi lity to liver damage due to differences in ethanol metabolism. Methods: We evaluated the role of three polymorphic genes related to alcoho l metabolism (CYP2EI) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in F lorence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control seri es of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism methods. Results: No difference was found in the frequency of the CYP2E1 RsaI c2 all ele (2.5% among alcoholics and 4.7% among controls) and the DraI C allele ( 6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 Al allele (15.8% and 13.3%) and the BI allele (10.8% and 8.6%). The p roportion of controls with a combined BI genotype (B1/B1 or B1/B2) was sign ificantly associated with smoking (p = 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14 %, respectively, homozygous S/S carriers. A significant association, howeve r, emerged in the group of alcoholics, with a five times higher risk for SI S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus po sitive alcoholics. Conclusions: Overall, our results provided no evidence of an increased susc eptibility to develop alcoholism that was associated with the three genotyp es investigated, either alone or in combination. An increased risk of devel oping liver cirrhosis for SIS homozygous carriers among alcohol-dependent p atients was observed for the first time.