SLC6A4 variation and citalopram response

D. A. Mrazek, A. J. Rush, J. M. Biernacka, D. J. O'Kane, J. M. Cunningham, E. D. Wieben, D. J. Schaid, M. S. Drews, V. L. Courson, K. A. Snyder, J. L. Black, R. M. Weinshilboum

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

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 hap- lotype 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.

Original languageEnglish (US)
Pages (from-to)341-351
Number of pages11
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number3
DOIs
StatePublished - Apr 5 2009

Keywords

  • Citalopram
  • Depression
  • SLC6A4
  • STAR d study

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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