Serotonin Transporter Gene Polymorphism and Major Depression / 신경정신의학

ABSTRACT

OBJECTIVE: Serotonin transporter(5-hydroxytryptamine transporter, 5-HTT) plays a critical role in the termination of serotonergic neurotransmission into the presynaptic neuron and represents an initial site of uptake inhibiting antidepressants, including tricyclic antidepressants and selective serotonin reuptake inhibitors. We investigated the possible association between the 5-HTT gene and major depression, and examined whether there are genotypic characteristics in 5-HTT gene that result in treatment nonresponsiveness to uptake inhibiting antidepressants. METHODS: 5-HTT gene polymorphisms are analyzed with the primers flanking the second intron and regulatory region from genomic DNA. We genotyped 142 patients with major depression and dysthymia, and 252 age and sex matched normal subjects. All individuals were Korean. RESULTS: We found no significant differences in the allele frequency(2 nd intron, p=0.941 promoter, p=0.122) between patients and controls. However, in association studies between antidepressant responsiveness in depressive patients and allele frequencies of 5-HTT gene polymorphism in intron2 and promoter regions, there was shown significant differences in both(p<0.0001, p=0.0028, respectively by Fisher exact test). CONCLUSIONS: These results suggest that there is no major effect of 5-HTT gene polymorphisms on the susceptibility to major depressions, while antidepressant nonresponding is related with genotypic alteration in 5-HTT gene.