The association of A-1438G and T102C polymorphisms in HTR2A and 120 bp duplication in DRD4 with alcoholic dependence in a northeastern Brazilian male population

Abstract

BackgroundAround the world, 3.3 million deaths are related to alcohol abuse. In Brazil, there are more than 4 million people with this behavior. Alcohol Dependence (AD) is a complex psychiatric disorder characterized by excessive alcohol consumption influenced by genetic and environmental factors. HTR2A and DRD4 are genes related to the serotonergic and dopaminergic systems and alterations in their sequences are associated with the etiology of AD. Our work analyzed the association between A-1438G (rs6311) and T102C (rs6313) polymorphisms in HTR2A and 120 bp duplication in DRD4 with the susceptibility to AD in that group of people. MethodsBlood samples were collected from 300 men from Northeastern Brazil (150 alcohol-dependents and 150 controls). After DNA extraction, the determination of HTR2A and DRD4 genotypes was performed through PCR-RFLP method. The allele and genotype frequencies and association of polymorphisms with AD were determined using chi-square and Fisher's exact test, as well as, odds ratio (OR) with confidence interval of 95%. Value of p < 0.05 was considered significant. ResultsSignificantly, the low education, intake of doses per day, smoking and a positive family background of alcoholics were predominant in alcoholics patients than controls (p < 0.05). The results showed no differences were found between polymorphisms in the HTR2A and DRD4 genes herein investigated with AD. However, we observed a significant association between the GG (GG: OR = 6.68; 95% CI: 2.85 to 15.68; p < 0.0001), CC (CC: OR = 4.34; 95% CI: 1.68 to 11.1; p = 0.003), AG + GG (AG + GG: OR = 5.96; 95% CI: 2.68 to 13.2; p = 0.0001) and, TC + CC (TC + CC: OR = 4.38; 95% CI: 1.79 to 10.6; p = 0.001) genotypes in the HRT2A gene and family background with susceptibility to AD in our population. ConclusionTherefore, we suggest that the homozygous and heterozygous genotypes of the A-1438G and T102C polymorphism in the HTR2A gene, together with the positive family AD history, may be associated with the development of AD in the northeastern Brazilian male population displaying a dominant inheritance model. Further work is strongly encouraged to confirm the role of these polymorphisms in AD.