Genetic factors of alcohol-dependence

Introduction. - Alcohol dependence is a complex and multifactorial disease resulting both from neurobiological mechanisms and environmental factors. It is frequently associated with comorbid psychiatric disorders or with specific personality or behavioral features. Although action can be taken on the environment in order to decrease the risk of the illness, current methods used to prevent or to treat this pathology show moderate efficacy: problematic consumption of ethanol in the general population as well as relapse rates under treatment in dependent patients remain indeed very high. Literature findings. - It is therefore of major importance to broaden our knowledge of alcohol dependence and its comorbidities so as to improve both their prevention and treatment. In this perspective, recent progress in the field of neurosciences may contribute to achieve this goal. Precisely, genetics is a promising way benefiting from many advances in genetic epidemiology, cellular and molecular biology, neuroimaging and pharmacology. In parallel with a better understanding of the neurobiology of addictions and associated behaviors, these techniques led to the identification of brain mechanisms in which a genetic variation may influence the individual vulnerability towards alcohol dependence. Moreover, there is growing evidence that alcoholism results from the interaction of genetic and environmental factors influencing both its expression and its course. Given the fact that alcohol-dependence seems highly heritable (50 to 60% of the variance in both men and women), this review assesses the role of some of the genomic regions linked with the disease, as well as the principal variants of candidate genes identified as specifically involved in the predisposition. Polymorphisms of genes influencing alcohol metabolism, GABAergic, dopaminergic and serotonergic neurotransmission seem, indeed, at stake in the development of alcohol-dependence and its related features such as personality, behavior, impulse control or craving. In the future, a better characterization of the links between genotypes and phenotypes will probably increase our ability to treat alcoholic patients. (C) L'Encephale, Paris, 2008.