Estudo de associação entre o polimorfismo de duplicação de 120 pb na região promotora do gene do receptor D4 de dopamina (DRD4) e a dependência do álcool em uma população do nordeste brasileiro

Abstract

Alcohol is a psychotropic drug with contributing properties in the addiction process. Its exaggerated use generates dependence on alcohol (AD), a disease that negatively affects society. Because it is a disease with multifactorial inheritance, AD has influence both of environmental factors and genetic factors. Studies show a key role of the dopaminergic system with drug abuse, including alcohol, with intensification around the DRD4 gene, encoding the dopamine D4 receptor. Considered one of the human genes with the highest number of polymorphisms, studies show that 120 bp doubling in the promoter region of the DRD4 gene may influence the transcription rate of the gene, however, the results of studies of association of dopamine receptors and alcoholism have been contradictory in different populations. Thus, the present study aims to evaluate whether the 120 bp polymorphism in the DRD4 gene is associated with alcohol susceptibility or

dependence in a male population in Northeast Brazil. As the investigation is a case- control study, they were genotyped by the PCR technique, followed by agarose gel

electrophoresis, samples of 143 alcoholics and 146 controls. The genotypic and allelic frequencies were submitted to chi-square, Fisher's exact and Odds Ratio tests with p <0.05. Results from the allelic distribution between the groups showed that the frequency of the short allele (S) was 24.13% in the alcoholic group and 22.60% in the control group, and the long allele (L) was 75.87% In the group of alcoholics and 77.40% among controls. The distribution of the genotypes and alleles of the 120 bp doubling polymorphism of the DRD4 gene did not differ significantly between alcoholics and controls, suggesting a negative association with susceptibility to alcohol dependence. Our findings revealed that alcoholics have a lower level of education compared to controls, and the association between alcoholics and smoking was significant (<0.0001). In addition, it is possible to observe that AD has a familial character, since relatives of alcohol abusers have a significantly higher frequency (<0.0001) of dependence than in non-alcohol dependent relatives. Further studies are needed to confirm these results and to clarify the role of the DRD4 gene in the risk of AD and in determining the factors that influence its genesis.