Serotonin Transporter Gene Polymorphsims and Its Phenotypic Characteristics Expressed in Platelet 3H-Serotonin Uptake Study in Korean Depressed Patients.
- Author:
Doh Kwan KIM
1
;
Min Young SEO
;
Shinn Won LIM
;
Hyeran KIM
;
Seonghwan KIM
Author Information
1. Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Serotonin transporter;
Gene polymorphism;
Pharmacodynamic characteristics;
Major depression
- MeSH:
Blood Platelets*;
Depression;
DNA;
Fluoxetine;
Genotype;
Healthy Volunteers;
Humans;
Introns;
Paroxetine;
Population Characteristics;
Promoter Regions, Genetic;
Regulatory Sequences, Nucleic Acid;
Serotonin Plasma Membrane Transport Proteins*;
Serotonin*;
Synaptic Transmission;
Tandem Repeat Sequences
- From:Journal of Korean Neuropsychiatric Association
2003;42(1):54-60
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVES: Serotonin transporter (5-HTT) is a key synaptic regulator of serotonergic neurotransmission and a major site of action of serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine or paroxetine. Two PCR-fomatted polymorphisms at this locus have been described, the first of which is a repeat sequence polymorphism located in the promoter region (5-HTT gene-linked polymorphic region, 5-HTTLPR), and the second is a variable number tandem repeat located in intron2 (STin2). 5-HTTLPR insertion/deletion polymorphism with long (l) and short (s) forms affects the transcriptional efficiency of 5-HTT transporter expression. We examined the pharmacodynamic characteristic of 5-HTT gene polymorphism in the patients with major depression, which was expressed in the peripheral platelet. METHODS: 5-HTT gene polymophisms and pharmacodynamic characteristics of 5-HTT in the platelet was measured in 41 patients with major depression defined by DSM IV criteria and 35 healthy normal volunteers. 5-HTT gene polymophisms were analyzed with the primers flanking the regulatory region and the second intron from genomic DNA. Pharmacodynamic characteristics of 5-HTT in the platelet was measured with [3H]-serotonin uptake study. The uptake of [3H]-serotonin was quantified with Vmax and Km value. RESULTS: We found that the Vmax value of 5-HTT in peripheral platelet was higher in the patients with s/s genotype (2.17 pmol/10(4) platelets/min, 1.53-3.90 pmol/10(4) platelets/min) than with s/l (1.73 pmol/10(4) platelets/min, 0.83-3.40 pmol/10(4) platelets/min) or l/l (1.0(4) pmol/10(4) platelets/min, 0.88-1.31 pmol/10(4) platelets/min) genotype of 5-HTTLPR. Normal subjects with s/s genotype also had significantly higher Vmax value than those with s/l or l/l genotype. However, STin2 genotype showed no significant association with Vmax or Km in both groups. CONCLUSIONS: These results suggest that allelic variation of 5-HTT gene affects the phenotypic expression of 5-HTT in human platelet, and may be linked with phenotypic heterogeneity in the antidepressant responsiveness in depressed patients. This is another different finding based on ethnic variation with respect to pharmacodynamic characteristics of 5-HTT gene polymorphism.
