Korean J Psychopharmacol.  2003 Sep;14(3):274-283.

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

• Kim DK
• Kim EJ
• Lim SW
• Kim H

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.

Keyword

Biogenic amine transporter; Serotonin transporter; Noradrenalin transporter; Dopamine transporter; Genetic polymorphism; Depression; Antidepressant response

MeSH Terms

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
3' Untranslated Regions
Antidepressive Agents
Biogenic Amines
DNA
Dopamine Plasma Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins