한국인 우울증 환자의 항우울제 반응성과 생체 아민 수송체 유전자 다형성의 연관성

Association between the Genetic Polymorphisms of the Biogenic Amine Transporters and the Antidepressant Responsiveness in Korean Depressed Patients

Objective : Serotonin transporter (5-H'IT) is a key synaptic regulator of serotonergic neurotransmission and a major site of action of most antidepressants. The functional polymorphism of 5-HIT gene is reported to be associated with antidepressant responsiveness. Norepinephrine transporter (NET) and dopamine transporter (DAT) are also the targets for antidepressant drugs, and these biogenic amine transporters share a similar structure and mode of action as 5-HIT. We investigated the association between genetic polymorphisms of biogenic amine transporters and antidepressant response. Methods : We genotyped 203 patients with major depressive disorder and 147 normal controls, using polymerase chain reaction (PCR) of genomic DNA with primers flanking the second intron and promoter regions of 5-HTT gene, and the 3' untranslated region of DAT, NET-I (Thr99Ile) and NET-8 (1287 G/A) polymorphism were characterized by amplification and restriction fragment length polymorphisms (RFLP) analysis. Results : VNTR polymorphism in the 3' untranslated region of DAT (p=0.020) was associated with a diagnosis of depression, but was influenced by age effect. We found that NET-8 polymorphism (p=0.015) in NET gene had significant associations with antidepressant response, as did the allelic variations of the promoter (p<0.0001) and intron2 (p=0.023) region in 5-HTT gene. The choice of drug had no effect on drug responsiveness. Conclusions : These results suggest that allelic variations of 5-HT'T and NET genes affect the antidepressant responsiveness. (Korean J Psychopharmacol 2003;14(3):274-283)