Please cite this article as follows: Mrazek DA, Rush AJ, Biernacka JM, O'Kane DJ, Cunningham JM, Wieben ED, Schaid DJ, Drews MS, Courson VL, Snyder KA, Black JL III, Weinshilboum RM. 2009. SLC6A4 Variation and Citalopram Response. Am J Med Genet Part B 150B:341–351.
SLC6A4 variation and citalopram response†
Article first published online: 10 JUL 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 3, pages 341–351, 5 April 2009
How to Cite
Mrazek, D.A., Rush, A.J., Biernacka, J.M., O'Kane, D.J., Cunningham, J.M., Wieben, E.D., Schaid, D.J., Drews, M.S., Courson, V.L., Snyder, K.A., Black, J.L. and Weinshilboum, R.M. (2009), SLC6A4 variation and citalopram response. Am. J. Med. Genet., 150B: 341–351. doi: 10.1002/ajmg.b.30816
- Issue published online: 17 MAR 2009
- Article first published online: 10 JUL 2008
- Manuscript Accepted: 20 MAY 2008
- Manuscript Received: 28 MAR 2008
- National Institute of Mental Health
- National Institutes of Health. Grant Number: N01MH90003
- NIH (“The Pharmacogenomics Research Network”). Grant Number: U01 GM61388
- PhRMA Foundation “Center of Excellence in Clinical Pharmacology Award”
- Cooper Family Foundation
- STAR*D study
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. © 2008 Wiley-Liss, Inc.