ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression

A. Ray, L. Tennakoon, J. Keller, J. E. Sarginson, H. S. Ryan, G. M. Murphy, L. C. Lazzeroni, M. H. Trivedi, J. H. Kocsis, C. Debattista, A. F. Schatzberg

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Abstract

The hypothesis that allelic variation in the multidrug resistance-1 (MDR1 or ABCB1) gene encoding the P-glycoprotein (P-gp) blood-brain barrier efflux pump is associated with remission and side effects was tested in chronic major depression patients treated with P-gp substrates. In 83 patients from the REVAMP trial, frequency of and time to remission as well as side effects was tested among genotype groups at 6 ABCB1 single nucleotide polymorphisms (SNPs). These six SNPs are significantly associated with remission and time to remission, with minor allele carriers on rs2235040 and rs9282564 attaining statistical significance after controlling for the other ABCB1 SNPs. The six ABCB1 SNPs are also significantly associated with the average side effects. However, here common homozygotes on rs2235040 and rs9282564 demonstrated significantly higher side effects after controlling for the effects of the other ABCB1 SNPs. These findings confirm and extend previous observations that minor alleles of two ABCB1 SNPs predict remission to treatment with substrates and demonstrate that common homozygotes on these SNPs experience greater side effects. Results point to the potential importance of ABCB1 variation for personalized medicine approaches to treating depression.

Original languageEnglish (US)
Pages (from-to)332-339
Number of pages8
JournalPharmacogenomics Journal
Volume15
Issue number4
DOIs
StatePublished - Aug 25 2015

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P-Glycoprotein
Single Nucleotide Polymorphism
Homozygote
Alleles
Precision Medicine
Multiple Drug Resistance
Blood-Brain Barrier
Genotype
Genes

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Ray, A., Tennakoon, L., Keller, J., Sarginson, J. E., Ryan, H. S., Murphy, G. M., ... Schatzberg, A. F. (2015). ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression. Pharmacogenomics Journal, 15(4), 332-339. https://doi.org/10.1038/tpj.2014.72

ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression. / Ray, A.; Tennakoon, L.; Keller, J.; Sarginson, J. E.; Ryan, H. S.; Murphy, G. M.; Lazzeroni, L. C.; Trivedi, M. H.; Kocsis, J. H.; Debattista, C.; Schatzberg, A. F.

In: Pharmacogenomics Journal, Vol. 15, No. 4, 25.08.2015, p. 332-339.

Research output: Contribution to journalArticle

Ray, A, Tennakoon, L, Keller, J, Sarginson, JE, Ryan, HS, Murphy, GM, Lazzeroni, LC, Trivedi, MH, Kocsis, JH, Debattista, C & Schatzberg, AF 2015, 'ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression', Pharmacogenomics Journal, vol. 15, no. 4, pp. 332-339. https://doi.org/10.1038/tpj.2014.72
Ray A, Tennakoon L, Keller J, Sarginson JE, Ryan HS, Murphy GM et al. ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression. Pharmacogenomics Journal. 2015 Aug 25;15(4):332-339. https://doi.org/10.1038/tpj.2014.72
Ray, A. ; Tennakoon, L. ; Keller, J. ; Sarginson, J. E. ; Ryan, H. S. ; Murphy, G. M. ; Lazzeroni, L. C. ; Trivedi, M. H. ; Kocsis, J. H. ; Debattista, C. ; Schatzberg, A. F. / ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression. In: Pharmacogenomics Journal. 2015 ; Vol. 15, No. 4. pp. 332-339.
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