Journal Article10.1067/MCP.2001.114164
Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects.
Ingolf Cascorbi,Thomas Gerloff,Andreas Johne,Christian Meisel,Sven Hoffmeyer,Matthias Schwab,Elke Schaeffeler,Eichelbaum Michel,Ulrich Brinkmann,Ivar Roots +9 more
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TL;DR: P‐glycoprotein, the gene product of MDR1, confers multidrug resistance against antineoplastic agents but also plays an important role in the bioavailability of common drugs in medical treatment.
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Abstract: Background
P-glycoprotein, the gene product of MDR1, confers multidrug resistance against antineoplastic agents but also plays an important role in the bioavailability of common drugs in medical treatment. Various polymorphisms in the MDR1 gene were recently identified. A silent mutation in exon 26 (C3435T) was correlated with intestinal P-glycoprotein expression and oral bioavailability of digoxin.
Objective
We wanted to establish easy-to-use and cost-effective genotyping assays for the major known MDR1 single nucleotide polymorphisms and study the allelic frequency distribution of the single nucleotide polymorphisms in a large sample of volunteers.
Methods
In this study, the distribution of the major MDR1 alleles was determined in 461 white volunteers with the use of polymerase chain reaction and restriction fragment length polymorphism.
Results
Five amino acid exchanges were found with allelic frequencies of 11.2% for Asn21Asp and 5.5% for Ser400Asn. Strikingly, in exon 21 three variants were discovered at the same locus: 2677G (56.4%), 2677T (41.6%), and 2677A (1.9%), coding for 893Ala, Ser, or Thr. A novel missense Gln1107Pro mutation was found in two cases (0.2%). The highest frequencies were observed for intronic and silent polymorphisms; C3435T occurred in 53.9% of the subjects heterozygously, and 28.6% of individuals were homozygous carriers of 3435T/T with functionally restrained P-glycoprotein.
Conclusion
This study provides the first analysis of MDR1 variant genotype distribution in a large sample of white subjects. It gives a basis for large-scale clinical investigations on the functional role of MDR1 allelic variants for bioavailability of a substantial number of drugs.
Clinical Pharmacology & Therapeutics (2001) 69, 169–174; doi: 10.1067/mcp.2001.114164
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Citations
Investigation of ABCB1 1236 and 2677 SNPs in patients with peptic ulcer.
Marta Żebrowska,Marcin Jażdżyk,Aleksandra Sałagacka,Mariusz Balcerczak,Robert Janiuk,Marek Mirowski,Ewa Balcerczak +6 more
TL;DR: The TT genotype and the mutated allele T for the polymorphisms 1236 and 2677 could increase peptic ulcer risk and ABCB1 1236 polymorphism may also be associated with an increased likelihood of H. pylori infection development, especially in women.
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Effect of ABCB1 haplotypes on the pharmacokinetics and renin-inhibiting effect of aliskiren
TL;DR: Aliskiren peak plasma concentration and area under the plasma concentration–time curve from 0 h to infinity in Participants homozygous for the TTT haplotype to those in participants homozygously for the CGC haplotype were 1.14 (0.66, 1.96; P = 0.631) and 1.01 ( 0.58, 1.) respectively.
Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole and gastroesophageal symptoms in Japanese renal transplant recipients classified as CYP2C19 extensive metabolizers and treated with tacrolimus.
M. Miura,Shigeru Satoh,Hitoshi Tada,M Saito,Hideaki Kagaya,Kazuyuki Inoue,Yoshinori Sagae,S Kanno,M Ishikawa,Tomonori Habuchi,Takehiro Suzuki +10 more
- 01 Dec 2006
TL;DR: In this paper, the implication of the ABCB1 C3435T polymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus was investigated.
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Pharmacogenomics and Personalized Medicine for Cancer
Dipali Dhawan,Harish Padh +1 more
- 01 Jan 2013
TL;DR: This chapter provides an overview of the well-studied molecular markers for efficacy and toxicity of cancer therapeutics and also discusses the evolution of the field of companion diagnostics in cancer.
9
Influence of ABCB1 polymorphisms on the pharmacokinetics and toxicity of lenalidomide in patients with multiple myeloma
TL;DR: It is shown that lenalidomide pharmacokinetics is influenced by the ABCB1 3435C>T polymorphism, which could be useful to individualize dosage design and reduce unexpected toxicity.
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