SLC6A4 variation and citalopram response

Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):341-51. doi: 10.1002/ajmg.b.30816.


The influence of genetic variations in SLC6A4 (serotonin transporter gene) on citalopram treatment of depression using the Sequenced Treatment to Relieve Depression (STAR*D) sample was assessed. Of primary interest were three previously studied polymorphisms: 1) the VNTR variation of the second intron, 2) the indel promoter polymorphism (5HTTLPR or SERT), and 3) a single nucleotide polymorphism (SNP) rs25531. Additionally, SLC6A4 was resequenced to identify new SNPs for exploratory analyses. DNA from 1914 subjects in the STAR*D study were genotyped for the intron 2 VNTR region, the indel promoter polymorphism, and rs25531. Associations of these variants with remission of depressive symptoms were evaluated following citalopram treatment. In white non-Hispanic subjects, variations in the intron 2 VNTR (point-wise P = 0.041) and the indel promoter polymorphism (point-wise P = 0.039) were associated with remission following treatment with citalopram. The haplotype composed of the three candidate loci was also associated with remission, with a global p-value of 0.040 and a maximum statistic simulation p-value of 0.0031 for the S-a-12 haplotype, under a dominant model. One SNP identified through re-sequencing the SLC6A4 gene, Intron7-83-TC, showed point-wise evidence of association, which did not remain significant after correction for the number of SNPs evaluated in this exploratory analysis. No associations between these SLC6A4 variations and remission were found in the white Hispanic or black subjects. These findings suggest that multiple variations in the SLC6A4 gene are associated with remission in white non-Hispanic depressed adults treated with citalopram. The mechanism of action of these variants remains to be determined.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Black or African American / genetics
  • Citalopram / therapeutic use*
  • Clinical Trials as Topic
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics*
  • Female
  • Gene Frequency
  • Genetic Variation
  • Haplotypes
  • Hispanic or Latino / genetics
  • Humans
  • Introns
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Minisatellite Repeats
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Remission Induction
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sequence Analysis, DNA
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Treatment Outcome
  • White People / genetics


  • Antidepressive Agents, Second-Generation
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Citalopram