Abstract:
BACKGROUND:P-glycoprotein (P-gp) is a multidrug efflux transporter that has a defined role in the absorption and disposition of drugs. Many studies have investigated the potential influence of ABCB1 polymorphisms on the disposition of its substrates. However, there remains significant controversy regarding the role of these polymorphisms. Our aim was to generate a P-gp expression system for single nucleotide polymorphisms (SNPs) and the reference sequence to assess the functional significance of these variants on transport. MATERIALS AND METHODS:P-gp reference, a P-gp ATPase deficient mutant (G534D) and a triple SNP variant of P-gp (1236C>T, 2677G>T, and 3435C>T) were expressed in Xenopus laevis oocytes and used to assess the influence of these SNPs on transport of digoxin and imatinib. The inhibition of P-gp-mediated transport in Caco-2 cells and oocytes was also assessed. RESULTS:No effect of the triple SNP variant of P-gp on molecular transport of digoxin or imatinib was observed. The rank order of inhibition of P-gp in Caco-2 cells and ABCB1-injected oocytes was tariquidar>elacridar>PSC-833>laniquidar>cyclosporine>verapamil>dipyridamole. CONCLUSION:These data suggest there is no functional consequence of these SNPs for molecular transport of model substrates or inhibition by model inhibitors for P-gp. Transporter-injected oocytes may be a useful tool for probing the mechanism for unexplained drug-drug interactions or to characterize therapeutic transport inhibitors.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Dickens D,Owen A,Alfirevic A,Pirmohamed Mdoi
10.1097/FPC.0b013e328360d10csubject
Has Abstractpub_date
2013-06-01 00:00:00pages
314-23issue
6eissn
1744-6872issn
1744-6880pii
01213011-201306000-00003journal_volume
23pub_type
杂志文章abstract::CYP2J2 and CYP2C8 metabolize arachidonic acid (AA) to cis-epoxyeicosatrienoic acids (EETs), which play a central role in regulating renal tubular fluid-electrolyte transport and vascular tone. We hypothesized that functionally relevant polymorphisms in the CYP2J2 or CYP2C8 genes influence hypertension risk. We examine...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200501000-00002
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:Individual differences in drug efficacy and toxicity remain an important clinical concern. We investigated copy number variation (CNV) frequencies for pharmacogenes using The Cancer Genome Atlas dataset. MATERIALS AND METHODS:One hundred and fifty-two pharmacogenes were selected from liver hepatocellular car...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000097
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:The prototypical atypical antipsychotic agent, clozapine, is more efficacious for refractory schizophrenia than the 'typical' antipsychotics, but the mechanism underlying this enhanced efficacy is still under investigation. Since 2002, at least 22 association studies have shown that the DTNBP1 can be associat...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e32832b9cfc
更新日期:2009-06-01 00:00:00
abstract:OBJECTIVE:Lung cancer, particularly the non-small-cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death worldwide. Several functional polymorphisms in inflammatory cytokine genes, such as IL1B, IL6, IL12A, IL13 and IL16, have been associated with the risk of NSCLC. The aim of this study was to ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000307
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVES:We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF). METHODS:A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000042
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVES:This study aimed to explore the influence of variation in DRD2, DRD3, CYP2D6, CYP3A4, and CYP3A5 genes on treatment resistance to typical neuroleptics in a Brazilian sample of patients with schizophrenia. METHODS:One polymorphism at DRD2 gene, five at DRD3, 24 at CYP2D6, nine at CYP3A4 gene, and one at CYP3...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328301a763
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND/AIM:Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 (CYP) enzymes. The aim of this study was to investigate whether single-nucleotide polymorphisms in the POR gene were correlated with interindividual variations in CYP2B6 activity, as measured by bupropi...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000190
更新日期:2016-02-01 00:00:00
abstract::The serotonin (5-HT) 1A receptor has been found to be dysregulated in prefrontal cortex and other brain regions in schizophrenia, and 5-HT1A receptor levels in the amygdala have been related to negative schizophrenia symptoms. We have assessed the impact of the functional C-1019G variant of the 5-HT1A receptor on the ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e328311a917
更新日期:2009-01-01 00:00:00
abstract::Endocrine disrupters, such as persistent organohalogen pollutants (POPs) may cause hypospadias, which is a common congenital anomaly in males, affecting 0.2-0.7%. We hypothesized that hypospadias incidence would be high among Greenlanders, who are one of the most POP exposed populations on earth through consumption of...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000199497.01101.93
更新日期:2006-05-01 00:00:00
abstract::The 1976C>T polymorphism in the adenosine A2A receptor gene (ADORA2A) modulates the psychological response to administration of the adenosine receptor antagonist caffeine. We quantified the vascular response to adenosine and caffeine to determine the relevance of this variant allele in the physiological response to th...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32803fb78f
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:The mammalian target of rapamycin (m-TOR) inhibitor sirolimus is an immunosuppressive drug used in kidney transplantation. m-TOR binds with Raptor and phosphorylates p70S6 kinase, a protein involved in numerous cell signalling pathways. We examined the association of candidate polymorphisms in m-TOR, Raptor ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FPC.0b013e328357359d
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:Studies found a strong association between allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000319
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVE:Exemestane is a third-generation aromatase inhibitor used in the treatment of breast cancer in postmenopausal women. Reduction to form 17-dihydroexemestane and subsequent glucuronidation to exemestane-17-O-glucuronide is a major pathway for exemestane metabolism. The goal of this study was to analyze 17-dihyd...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833b04af
更新日期:2010-10-01 00:00:00
abstract:OBJECTIVE:The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter, namely the variable number tandem repeat polymorphism (TS VNTR) and the intrarepeat G to C single n...
journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章
doi:10.1097/01.fpc.0000230412.89973.c0
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVE:The effects of various polymorphisms in cytochrome P450 (CYP) enzyme and transporter genes on the pharmacokinetics (PK) of simvastatin were evaluated in healthy Korean men. METHODS:Plasma concentration data for simvastatin and simvastatin acid were pooled from four phase I studies comprising 133 participants...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0000000000000176
更新日期:2015-12-01 00:00:00
abstract::Small heterodimer partner 1 (SHP1, NR0B2) is a member of the superfamily of nuclear receptors (NRs). Even if this orphan receptor, unlike other NRs, lacks the DNA-binding domain, it is capable of regulating transcription by repressing the activity of other NRs by direct protein-protein interaction. Accordingly, SHP1 i...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000310
更新日期:2017-11-01 00:00:00
abstract::TPMT and NUDT15 polymorphisms are major determinants of tolerance to thiopurine drugs used in leukemias and nonmalignant immunologic disorders. We adopted an extreme discordant phenotype approach to explore the impact of Native American versus European ancestry on the distribution of TPMT and NUDT15 polymorphisms, and...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000388
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:We tested the effect of kidney-specific multidrug resistance-related protein (MRP2, ABCC2) deficiency on renal organic solute disposition as well as on renal protein and gene expression. Furthermore, we investigated whether a particular kidney donor ABCC2 genotype is associated with delayed graft function in...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328328d4e9
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:Paraoxonase-1 (PON1) is synthesized in the liver and is bound to high-density lipoprotein particles in blood. PON1 protects against the development of atherosclerosis by metabolizing proatherogenic-oxidized lipids. The Southeastern USA (excluding Florida) has the country's highest age-adjusted mortality rate ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834cebc6
更新日期:2011-12-01 00:00:00
abstract::The present study aimed to determine whether a polymorphism in CYP3A5, encoding the major CYP3A enzyme in the human kidney, is associated with blood pressure in Caucasians. A homogenous group of 115 young, white male students with normal or mildly elevated, but untreated blood pressure was included. Blood pressure was...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000175599.49764.98
更新日期:2005-10-01 00:00:00
abstract:OBJECTIVE:Glutathione S-transferase enzymes (GSTs; EC: 2.5.1.18) constitute the principal phase II superfamily, which plays a key role in cellular detoxification. GST genes are organized in chromosomal clusters; most of these genes are polymorphic, mainly due to single nucleotide substitutions. Different studies proved...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328349da4d
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:For prevention of joint destruction in rheumatoid arthritis, optimal management of therapy with disease-modifying antirheumatic drugs is essential. Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of rheumatoid arthritis to achieve a more efficient activity control with minimized a...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000236326.80809.b1
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:Recently, the minor allele of the rs13064411A>G polymorphism in the WD repeat domain 52 (WDR52) gene was associated with increased statin-induced proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and with LDL cholesterol response to statins. PCSK9 promotes LDL receptor degradation, leading to incre...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000120
更新日期:2015-03-01 00:00:00
abstract::We recently showed an association between the FCGR3A V/F polymorphism and the biological response [assessed on the basis of a C-reactive protein (CRP) concentration decrease] to infliximab in Crohn's disease. The CRP and FCGR3A genes are located on the same 1q23 locus. The present study aimed: (i) to exclude a linkage...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000182776.57437.d8
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:5-Hydroxytryptamine 3 (5-HT3) receptors mediate the fast excitatory neurotransmission of serotonin. In this study, we have characterized the effects of four naturally occurring, nonsynonymous variants of the human 5-HT3B subunit on expression and signalling properties of heteromeric 5-HT3AB receptors. METHO...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328310f950
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVES:Immediate reactions - particularly anaphylactic ones - to betalactams are the most common adverse reactions to antibiotics mediated by a specific immunologic mechanism. The genetic risk factors influencing these mechanisms are poorly known. We aimed to evaluate the association between immediate allergic reac...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000230409.00276.44
更新日期:2006-10-01 00:00:00
abstract::Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including human squamous cells of the head and neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been described...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200503000-00004
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:Corticotropin-releasing hormone receptor (CRHR)-2 participates in smooth muscle relaxation response and may influence acute airway bronchodilator response to short-acting beta2-agonist treatment of asthma. We aim to assess associations between genetic variants of CRHR2 and acute bronchodilator response in ast...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FPC.0b013e3282fa760a
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Gene expression is regulated by trans-acting transcription factors and microRNAs (miRNAs) through interactions with their respective cis-regulatory elements. The effects that drugs induce result from complex interactions in pathways downstream from their primary targets. These interactions, from gene regulat...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000111
更新日期:2015-03-01 00:00:00
abstract:OBJECTIVE:We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. PARTICIPANTS AN...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000298
更新日期:2017-10-01 00:00:00