MRP1 Polymorphisms Associated With Citalopram Response in Patients With Major Depression

• DOI: 10.1097/jcp.0b013e3181d2ef42
• Publication Date: 2010-03-05T06:48:34Z
• Authors: 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
• Keywords: Citalopram; Linkage Disequilibrium; SNP

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