Genetic and Pharmacogenetic Aspects of Alcohol-Dependence

Nicolas      Ramoz; Gunter      Schumann; Philip      Gorwood

Abstract

Alcohol dependence is a frequent and complex disorder involving both genetic (h2≉ 0.5) and environmental factors. The definition of what is inherited with alcohol dependence is still unknown. Shared liability has been detected with other addictive disorders (mainly nicotine dependence), and certain psychiatric disorders (such as bipolar disorder) and/or personality disorders (specifically antisocial personality). Such a broad spectrum may also explain the development of antidepressants, mood regulators and/or anti-impulsive drugs in the treatment of alcohol dependence. Genome wide scans, analyses of alcohol metabolism and reward circuits have identified many candidate genes or locations. Some genes linked to the reward pathway of alcohol, may have pharmacogenetic relevancy, such as the GABRA6 gene (regarding the role of benzodiazepine in alcohol withdrawal), SLC6A4 gene (as serotonin reuptake inhibitors may reduce alcohol intake in subgroups of patients), CB1 gene (because the CB1 agonists modify alcohol consumption, at least in rodents), and the OPRM1 gene (the 118G allele being associated with increased chances of Naltrexone efficacy). High-throughput approach for genotyping of polymorphisms, transcriptomics, and proteomics are useful tools that will help to identify susceptibility and protection genes for alcohol diseases. Together, these tools could be used to develop a rational pharmacogenomics strategy to test specific individual treatment for alcohol dependence.

Keywords: Opioids, Flushing Syndrome, DRD2 receptors, neurotransmitter, CB1 gene, MAP-kinase

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