MRP1 polymorphisms associated with citalopram response in patients with major depression

Sung Hee Lee, Min-Soo Lee, Ji Hyun Lee, So Won Kim, Rhee Hun Kang, Myoung Jin Choi, Sang Jin Park, Se Joo Kim, Jae Myun Lee, Susan P.C. Cole, Min Goo Lee

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Abstract

Multidrug resistance protein 1 (MRP1, ABCC1) transports antidepressive agents in the endothelial cells of the blood-brain barrier. Therefore, polymorphisms in the MRP1 gene may affect the treatment response of antidepressants. This study was aimed to identify the association between genetic variations in MRP1/ABCC1 and the therapeutic response to the antidepressant citalopram One hundred and twenty-three patients who had been treated with Citalopram monotherapy to control their major depressive disorder were recruited, and genotype data from 64 patients who had completed their 8-week follow-up were evaluated together with those from 100 controls. Nine MRP1 single nucleotide polymorphisms (SNPs) showing more than 5% allele frequency in the Korean population were analyzed. The c.4002G>A, a synonymous SNP in exon 28, showed a strong association with the remission state at 8 weeks (P = 0.005, odds ratio [OR], 4.7, 95% confidence interval [CI], 1.5∼14.7). The c.4002G>A forms a linkage disequilibrium block with 3 other SNPs including c.5462T>A in the 3' untranslated region. Accordingly, the haplotype showed a significant association with the remission state (P = 0.014). Subsequent molecular studies also supported the association between these MRP1 polymorphisms and the citalopram response. Thus, kinetic studies using MRP1enriched membrane vesicles revealed that Citalopram is a substrate of MRP1 (Km = 1.99 μM, Vmax = 137 pmol/min per milligram protein). In addition, individuals with c.4002G>A or c.5462T>A polymorphisms showed higher MRP1 mRNA levels in peripheral blood cells. These results suggest that MRP1. polymorphisms may be a predictive marker of citalopram treatment in major depression.

Original languageEnglish
Pages (from-to)116-125
Number of pages10
JournalJournal of Clinical Psychopharmacology
Volume30
Issue number2
DOIs
Publication statusPublished - 2010 Apr 1
Externally publishedYes

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Keywords

  • Abc transporter
  • Citalopram
  • Major depressive disorder
  • MRP1/ABCC1
  • Remission

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Lee, S. H., Lee, M-S., Lee, J. H., Kim, S. W., Kang, R. H., Choi, M. J., Park, S. J., Kim, S. J., Lee, J. M., Cole, S. P. C., & Lee, M. G. (2010). MRP1 polymorphisms associated with citalopram response in patients with major depression. Journal of Clinical Psychopharmacology, 30(2), 116-125. https://doi.org/10.1097/JCP.0b013e3181d2ef42