title: Serotonin transporter genotype and function in relation to antidepressant response in Koreans.
abstract: BACKGROUND
  Serotonin transporter (5-HTT) gene polymorphisms are linked with antidepressant response to selective serotonin reuptake inhibitor drugs (SSRIs), though the favorable allelic variant differs by ethnic group (Caucasian versus Korean or Japanese). In Caucasian patients, response also is linked to measures of platelet 5-HTT function.
  
  
  OBJECTIVE
  Here, we study both 5-HTT gene polymorphisms and 5-HTT function as determinants of antidepressant response to SSRIs in Korean patients.
  
  
  METHODS
  We enrolled 99 patients with major depression and 48 control subjects. For statistical power, both samples were enriched with the l/l 5-HTTLPR polymorphism, which is uncommon in Koreans. Patients were treated with fluoxetine or sertraline. Response was assessed at 6 weeks. Subjects were genotyped for s/l polymorphism in the 5-HTT promoter region (5-HTTLPR). Platelet 5-HTT activity was determined as maximal uptake rate (Vmax) and affinity constant (Km).
  
  
  RESULTS
  Response was differentially associated with the s allele of 5-HTTLPR, which also was significantly associated with Vmax. These associations are opposite to those reported in Caucasian populations. Responders had significantly higher Vmax and Km than nonresponders. In Koreans as well as Caucasians, high Vmax is related to antidepressant response to SSRIs, though the 5-HTTLPR polymorphism associations with both response and function differ by ethnicity.
  
  
  CONCLUSIONS
  Both ethnicity and function must be considered in evaluating candidate gene biomarkers of response to SSRIs in depression.
authors.affiliation: Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Korea.
authors.forename: Woojae
authors.initials: W
authors.lastname: Myung
authors.forename: Shinn-Won
authors.initials: SW
authors.lastname: Lim
authors.forename: Seonwoo
authors.initials: S
authors.lastname: Kim
authors.forename: Hyeran
authors.initials: H
authors.lastname: Kim
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chung
authors.forename: Min Young
authors.initials: MY
authors.lastname: Seo
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Carroll
authors.forename: Doh Kwan
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D056910:Republic of Korea; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020280:Sertraline / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D005473:Fluoxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline