Associação entre polimorfismos do gene triptofano hidroxilase 2 e a depressão de início tardio

Abstract

Major depression is one of the most common psychiatric disorders, and in elderly its prevalence impact in terms of high rates of suicide and worst prognosis in comorbidities. Major depression that happens after 60 years is considered late-onset depression. The population above this age has increased significantly in Brazil, and it is estimated that in 2025 will reach approximately 32 million elderly. Many studies suggest that early-onset depression and late-onset depression have many different clinical and also genetic aspects. Some tryptophan hydroxylase type II gene (TPH2) variants have been associated with many psychiatric disorders in special with the major depression. TPH2 is the rate-limiting enzyme in the biosynthesis of serotonin. Polymorphisms in TPH2 might promote changes in brain serotonin synthesis. Thus, we aimed to investigate the frequencies of TPH2 polymorphisms in a group of elderly patients with late-onset depression in a brazilian population and whether these frequencies are associated with depressive events. Here, we genotyped eight tagSNPs from the gene TPH2 in 84 samples with late-onset depression and 79 controls. Genotyping was performed using TaqMan Real Time PCR. Unphased 3.0.13 program was used for genetic association. Overall, we identified an association between tagSNPs rs4565946 (C/T) and rs11179000(A/A) and late-onset depression. For allelic association of tagSNP rs11179000 we observed a strong association of allele A and risk of late-onset depression. Our findings suggest the involvement of genetic variants in the TPH2 gene in the etiology of late onset depression in brazilian population.