Associação de polimorfismos do gene da enzima Triptofano Hidroxilase 2 (TPH2) com a depressão

Abstract

Disease-gene association studies reported a relation between the Tryptophan Hydroxylase 2 (TPH2) and depression in different populations. However, some studies do not demonstrate this relationship. Being TPH2 a limiting enzyme in the rate of synthetic route of serotonin in the brain, many studies reported the polymorphisms of the TPH2 enzyme. Two huge projects, HapMap and 1000 genomes, organized the major part of these polymorphisms from the study of several populations becoming these data available. This work is aimed to develop a system to obtain possible predisposition markers of a disease from the correlation between epidemiological data and population frequencies of polymorphism. This study is based in the hypothesis that if in a population there is more frequency of a certain kind of pathology genetically determined, the variables involved should be more frequent and vice-versa. The model used was the involvement of variables of the TPH2 gene in the predisposition of depression. The data obtained with positive correlation in one of homozygous genotypes and in the allele of this homozygous suggested the presence of 10 polymorphisms (total 14,49%) possibly related to the development of depression. These data were compared to the literature involving case-control studies. In this work were studied 20 from 69 polymorphisms described to the TPH2 gene. With the exception of only one polymorphism, all the data obtained through the strategy proposed in here was similar to the literature, including the allele that is determinant to the predisposition of depression, when it is demonstrated the association. Therefore, we have proposed this strategy as an alternative to realize this kind of Genome-Wide Association studies without the necessity of a case control study, only using the epidemiological data from the disease, decreasing the time and the cost of this study.