1.Association between the Genetic Polymorphisms of the Biogenic Amine Transporters and the Antidepressant Responsiveness in Korean Depressed Patients.
Doh Kwan KIM ; Eui Jung KIM ; Shinn Won LIM ; Haeran KIM
Korean Journal of Psychopharmacology 2003;14(3):274-283
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.
3' Untranslated Regions
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Antidepressive Agents
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Biogenic Amines*
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Depression
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Depressive Disorder, Major
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Diagnosis
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DNA
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Dopamine Plasma Membrane Transport Proteins
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Humans
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Introns
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Norepinephrine Plasma Membrane Transport Proteins
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Polymerase Chain Reaction
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Polymorphism, Genetic*
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Polymorphism, Restriction Fragment Length
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Promoter Regions, Genetic
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Serotonin Plasma Membrane Transport Proteins
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Synaptic Transmission