Journal Article10.1097/01.FPC.0000178311.02878.83
Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>T affects mRNA stability.
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TL;DR: The abundant 3435C>T SNP appears to be a main factor in allelic variation of ABCB1 mRNA expression in the liver, by changing mRNA stability.
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Abstract: ObjectivesABCB1 (multidrug resistance 1 polypeptide, MDR1, Pgp) is a multispecific efflux transporter of drugs and xenobiotics. Among numerous polymorphisms in human ABCB1, the synonymous SNP 3435C>T has been associated with decreased mRNA and protein levels, via unknown mechanisms.MethodsTo search
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Citations
Influence of genetic polymorphisms on gefitinib pharmacokinetics and adverse drug reactions in non-small cell lung cancer patients
Munisamy Murali,Mallayasamy Surulivelrajan,Udupa Karthik S +2 more
Abstract: Abstract Gefitinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in the treatment of non-small cell lung cancer (NSCLC). It is metabolized extensively in the liver by enzymes encoded by CYP3A4 , CYP2D6, and CYP3A5 and is the substrate of membrane transporters including ABCB1 and ABCG2 . Evidence shows that single-nucleotide polymorphisms (SNPs) in these metabolizing and transporting genes contribute to the inter-individual variability in gefitinib response and development of gefitinib-induced adverse drug reactions (ADRs). This narrative review identifies the existing literature exploring the impact of SNPs on plasma gefitinib concentration and ADRs in patients with NSCLC receiving gefitinib therapy. SNPs were identified in drug-metabolizing enzyme coding genes, including CYP3A4, CYP2D6, CYP3A5, and other CYP homologs, drug transporters including ABCB1, ABCG2, SLCO1B1 and other genes, including UGT1A7 and FOXO3. Current research has not identified any genetic association between specific SNPs in ABCB1, OATP1B1, and UGT1A7 and the pharmacokinetics of gefitinib. Additionally, most of these studies focused on individual SNP associations; however, it may be more important to consider them in combination to better understand their collective impact on gefitinib ADR. Hence, further comprehensive research is essential to examine these genetic variants across different ethnic groups, monitor the drug-drug interactions, and study the phenoconversion to draw definitive conclusions about the pharmacokinetics of gefitinib. This could lead to the development and implementation of a genotyping-based approach for gefitinib dosage optimization in clinical settings.
Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment
Vadim Yuferov,Orna Levran,Dmitri Proudnikov,David A. Nielsen,David A. Nielsen,Mary Jeanne Kreek +5 more
TL;DR: In genomewide and multigene association studies, it is found association of several new genes and new variants of known genes with heroin addiction, and the development and application of a novel technique: molecular haplotyping for studies in genetics of drug addiction.
Association of ABCB1/MDR1 polymorphisms in patients with glucocorticoid-induced osteonecrosis of the femoral head: Evidence for a meta-analysis.
Zifei Zhou,Yingqi Hua,Junjian Liu,Dongqing Zuo,Hongsheng Wang,Quanchi Chen,Longpo Zheng,Zhengdong Cai +7 more
TL;DR: The meta-analysis revealed that 3435T allele and ABCB1 2677T/A allele may decrease the risks of GC-induced ONFH.
Pharmacogenomics of the RNA World: Structural RNA Polymorphisms in Drug Therapy
Wolfgang Sadee,Danxin Wang,Audrey C. Papp,Julia K. Pinsonneault,Ryan M. Smith,Robert A. Moyer,Andrew D. Johnson +6 more
TL;DR: The role of srSNPs in drug metabolism, transport, and response, and an understanding of the nature and diversity of SrSNPs and rSNPs enables clinical scientists to evaluate genetic biomarkers is focused on.
OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings.
Aline Hajj,Lucine Halepian,Nada El Osta,Nada El Osta,Georges Chahine,Joseph Kattan,Lydia Rabbaa Khabbaz +6 more
TL;DR: Age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h, which could help increase the effectiveness of Morphine treatment and enhance the QOL of patients in regards to personalized medicine.
References
Mfold web server for nucleic acid folding and hybridization prediction
TL;DR: The objective of this web server is to provide easy access to RNA and DNA folding and hybridization software to the scientific community at large by making use of universally available web GUIs (Graphical User Interfaces).
Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
Sven Hoffmeyer,Oliver Burk,O. von Richter,H. P. Arnold,Jürgen Brockmöller,Andreas Johne,Ingolf Cascorbi,Thomas Gerloff,Ivar Roots,Eichelbaum Michel,Ulrich Brinkmann +10 more
TL;DR: A significant correlation of a polymorphism in exon 26 (C3435T) of MDR-1 with expression levels and function is observed and this polymorphism is expected to affect the absorption and tissue concentrations of numerous other substrates of M DR-1.
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Identification of functionally variant MDR1 alleles among European Americans and African Americans
Richard B. Kim,Richard B. Kim,Brenda F. Leake,Brenda F. Leake,Edna F. Choo,Edna F. Choo,George K. Dresser,George K. Dresser,Samir V. Kubba,Samir V. Kubba,Ute I. Schwarz,Ute I. Schwarz,Amanda Taylor,Amanda Taylor,H. G. Xie,H. G. Xie,Joel McKinsey,Joel McKinsey,Sheng Zhou,Sheng Zhou,Lu-Bin Lan,Lu-Bin Lan,John D. Schuetz,John D. Schuetz,Erin G. Schuetz,Erin G. Schuetz,Grant R. Wilkinson,Grant R. Wilkinson +27 more
TL;DR: Allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P‐glycoprotein function.
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Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor
Jubao Duan,Mark S. Wainwright,Josep M. Comeron,Naruya Saitou,Alan R. Sanders,Joel Gelernter,Pablo V. Gejman +6 more
TL;DR: Some synonymous mutations in the human DRD2 have functional effects and suggest a novel genetic mechanism, calling into question some assumptions made about synonymous variation in molecular population genetics and gene-mapping studies of diseases with complex inheritance, and indicate that synonymous variation can have effects of potential pathophysiological and pharmacogenetic importance.
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance.
Catia Marzolini,Catia Marzolini,Erik Paus,Erik Paus,Thierry Buclin,Thierry Buclin,Richard B. Kim,Richard B. Kim +7 more
TL;DR: SNPs in MDR1 in relation to population frequencies, drug levels, and phenotypes are outlined and issues relating to M DR1 haplotypes, environmental factors, and study design, as potential confounding factors of the observed MDR 1 polymorphism effect in vivo, are discussed.
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