Estudo de associação de polimorfismos dos genes gstm1, gstt1 e gstp1 com suscetibilidade ao uso abusivo do álcool em uma população do nordeste brasileiro

Abstract

Alcohol dependence (AD) is defined as a set of behavioral, cognitive and physiological phenomena that develop after frequent use of alcohol, culminating in a strong desire for consumption, difficulty controlling their use, tolerance, among others. Genetic factors are responsible for the variation in alcohol dependence in some groups and vulnerable individuals. Glutathione S-Transferases (GSTs) are a group of metabolizing phase II enzymes, which are, involved in detoxication of xenobiotics, among them the alcohol. Polymorphisms in coding genes of GSTs, GSTM1*0, GSTM1*0 and GSTP1 Ilel05Val (rs 1965), are associated with a decrease or loss of enzymatic function, leading to decreased detoxication capacity, leading to increased sensitivity to the effects o these genotoxins. This study looked for the analysis of the association of the polymorphisms GSTP1*0, GSTM1*0 and GSTP1 Ilel05Val (1965), in the susceptibility to the development of AD in a male population of the Brazilian Northeast, in a case-control study, which covered 138 alcoholics and 145 controls. The detection of polymorphisms was performed by multiplex PCR techniques (GSTM1 and GSTT1) and PCR-RFLP (GSTP1), followed by agarose gel electrophoresis. The genotyped frequencies were submitted to the chi-square test, Fisher’s exact and Odds Ratio with p<0.05. In the present investigation there was a positive association between low education and the harmful use of alcoholic beverages (p=0.05). Our findings demonstrate that individuals with a family history of abusive use of alcohol presented higher frequency in the alcoholic group compared to the control with p < 0.0001, suggesting that there is a heritable transmission of alcohol abuse disorders in our drinkers individuals. There were no statistical significance in any of the associations of the polymorphisms alone or combined with AD. In the analysis of the GSTP1*0 polymorphism among smoking alcoholics (31.65%) and smoking controls (55.56%) was statiscally significant when compared the two groups (p=0.02). The absence of risk association or protection from AD of the polymorphisms in this study, not excluding totally the possibility of association of these genes in the development of the AD.