Marcadores genéticos dopaminérgicos, serotoninérgicos y de la monoamino-oxidasa (MAO) relacionados con la adicción a los opiáceos, a la cocaína y al alcohol

Introduction: Genetics is a fast-growing field and is proving to be an important tool for making new discoveries about complex disorders such as addiction. The present work combines a study of the genetic association between VNTR polymorphisms, a family study and a study of the association between genetics and family in a sample of polydrug users addicted to alcohol, cocaine or opiates. Material and methods: Samples of cheek epithelial cells were collected from 302 polyconsumers and genotyped to observe the frequency of markers of the dopaminergic, serotoninergic and MAO pathways in opiate, cocaine and alcohol addictive disorders. VNTR polymorphisms were analyzed in DBH, DRD5 and TH genes in the dopaminergic pathway, in HTR1B, HTR1D, HTR2C and TPH genes in the serotoninergic pathway, and in MAO-A and MAO-B genes in the MAO pathway. Results: In the dopaminergic pathway a polymorphism of the TH gene was less frequent in individuals addicted exclusively to opiates and DBH gene polymorphisms were associated with a family history of mental illness in Cocaine+Opiates addicts. In the serotoninergic pathway HTR1B gene polymorphisms were associated with Alcohol+Cocaine+Opiates addiction and also with a family history of drug consumption in subjects addicted only to alcohol or cocaine and with a family history of alcohol consumption in Alcohol+Cocaine addicts. A HTR2C gene polymorphism was less frequent among Cocaine+Opiates addicts and was related with a family history of drug consumption in polydrug users. In the MAO pathway, one polymorphism was associated with addiction to cocaine or opiates and two with addiction to Alcohol+Opiates.MAO-A gene polymorphisms were also associated with a family history of alcohol consumption in subjects addicted exclusively to opiates and with a family history of alcohol consumption and mental illness in Alcohol+Cocaine addicts. Subjects with alcohol addiction were more likely to have a family history of consumption of alcohol, while cocaine addicts were more likely to have a family history of consumption of drugs other than alcohol. Surprisingly, the incidence of mental illness was lower among the families of polydrug users with opiate addiction. Conclusion: The present study highlights new associations between genetic markers and addiction to alcohol, cocaine and opiates among polydrug users. Some of these markers point towards a general vulnerability to addiction, while others seem to be associated with addiction to specific substances. Specific markers increase the risk of addiction, while others protect against addiction to certain substances. Further investigation is required to clarify and quantify the complex role of genetics in addictive disorders and to apply this knowledge to prevention (genetic counseling), diagnosis (genetic vulnerability diagnosis) and treatment (pharmacogenomics) of drug addiction.