Association between the Genetic Polymorphisms of the Biogenic Amine Transporters and the Antidepressant Responsiveness in Korean Depressed Patients.
- Author:
Doh Kwan KIM
1
;
Eui Jung KIM
;
Shinn Won LIM
;
Haeran KIM
Author Information
1. Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Biogenic amine transporter;
Serotonin transporter;
Noradrenalin transporter;
Dopamine transporter;
Genetic polymorphism;
Depression;
Antidepressant response
- MeSH:
3' Untranslated Regions;
Antidepressive Agents;
Biogenic Amines*;
Depression;
Depressive Disorder, Major;
Diagnosis;
DNA;
Dopamine Plasma Membrane Transport Proteins;
Humans;
Introns;
Norepinephrine Plasma Membrane Transport Proteins;
Polymerase Chain Reaction;
Polymorphism, Genetic*;
Polymorphism, Restriction Fragment Length;
Promoter Regions, Genetic;
Serotonin Plasma Membrane Transport Proteins;
Synaptic Transmission
- From:Korean Journal of Psychopharmacology
2003;14(3):274-283
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: Serotonin transporter (5-HTT) is a key synaptic regulator of serotonergic neurotransmission and a major site of action of most antidepressants. The functional polymorphism of 5-HTT 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-HTT. 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-1 (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-HTT and NET genes affect the antidepressant responsiveness.
