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MRP1 polymorphisms associated with citalopram response in patients with major depression

Authors
 Jung-Soo Lee  ;  Young Mee Lee  ;  Joo Young Kim  ;  Hyun Woo Park  ;  Sergio Grinstein  ;  John Orlowski  ;  Eunjoon Kim  ;  Kyung Hwan Kim  ;  Min Goo Lee 
Citation
 JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, Vol.30(2) : 116-125, 2010 
Journal Title
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
ISSN
 0271-0749 
Issue Date
2010
MeSH
Adult ; Aged ; Citalopram/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Depressive Disorder, Major/genetics* ; Depressive Disorder, Major/psychology ; Female ; Follow-Up Studies ; Gene Frequency/genetics ; Genetic Variation/genetics ; Humans ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Treatment Outcome ; Young Adult
Keywords
MRP1/ABCC1 ; citalopram ; remission ; major depressive disorder ; ABC transporter
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 approximately 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 MRP1-enriched membrane vesicles revealed that citalopram is a substrate of MRP1 (Km = 1.99 microM, 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.
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00004714-201004000-00004&LSLINK=80&D=ovft
DOI
10.1097/JCP.0b013e3181d2ef42
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Joo(김세주) ORCID logo https://orcid.org/0000-0002-5438-8210
Kim, So Won(김소원)
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Lee, Sung Hee(이성희)
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
Lee, Ji Hyun(이지현)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100828
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