Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects

Cascorbi, Ingolf; Gerloff, Thomas; Johne, Andreas; Meisel, Christian; Hoffmeyer, Sven; Schwab, Matthias; Schaeffeler, Elke; Eichelbaum, Michel; Brinkmann, Ulrich; Roots, Ivar

doi:10.1067/mcp.2001.114164

Cited by 672 publications

(481 citation statements)

References 20 publications

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“…CYP3A5*3 (6986A4G (rs776746)) and SLC22A1 (156T4C (rs1867351), 480G4C (rs683369), 1022C4T (rs2282143) and 1222A4G (rs628031)) genotyping was performed by PCR-RFLP, as previously described by Fukuen et al 34 and Itoda et al, 25 respectively. Similarly, ABCC2 (À24C4T (rs717620)) and ABCB1 (1236T4C (rs1128503), 2677G4T/A (rs2032582) and 3435T4C (rs1045642)) were genotyped as described by Naesens et al, 35 Wu et al, 36 Tanaka et al 37 and Cascorbi et al, 38 respectively. ABCG2 421C4A (rs2231142) was genotyped as described by Kobayashi et al, 39 and SLCO1B3 (334T4G (rs4149117)) as described by Tsujimoto et al 40 All genotype frequencies were tested for Hardy-Weinberg equilibrium.…”

Section: Measurement Of Plasma Im Concentrationmentioning

confidence: 99%

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

et al. 2010

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Imatinib mesylate (IM) trough concentration varies among IM-treated chronic myeloid leukemia (CML) patients. Although IM pharmacokinetics is influenced by several enzymes and transporters, little is known about the role of pharmacogenetic variation in IM metabolism. In this study, associations between IM trough concentration, clinical response and 11 single-nucleotide polymorphisms in genes involved in IM pharmacokinetics (ABCB1, ABCC2, ABCG2 CYP3A5, SLC22A1 and SLCO1B3) were investigated among 67 Japanese chronic phase CML patients. IM trough concentration was significantly higher in patients with a major molecular response than in those without one (P¼0.010). No significant correlations between IM trough concentration and age, weight, body mass index or biochemical data were observed. However, the dose-adjusted IM trough concentration was significantly higher in patients with ABCG2 421A than in those with 421C/C (P=0.015). By multivariate regression analysis, only ABCG2 421A was independently predictive of a higher dose-adjusted IM trough concentration (P¼0.015). Moreover, previous studies have shown that the ABCG2 421C4A (p.Q141K) variant is prevalent among Japanese and Han Chinese individuals and less common among Africans and Caucasians. Together, these data indicate that plasma IM concentration monitoring and prospective ABCG2 421C4A genotyping may improve the efficacy of IM therapy, particularly among Asian CML patients.

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Section: Measurement Of Plasma Im Concentrationmentioning

confidence: 99%

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

et al. 2010

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“…The first genetic polymorphism of MDR1 to be identified was a G2677T variant isolated from human adrenal, liver, and kidney samples that results in an Ala893Ser change in Pglycoprotein (19,20 (21)(22)(23)(24)(25)(26)(27)(28). Table I gives a summary of 19 segregating sites, resulting in 20 coding region variants identified in a population of 247 healthy individuals of different ethnic backgrounds (22).…”

Section: Genetic Variation In Mdr1mentioning

confidence: 99%

Functional Implications of Genetic Polymorphisms in the Multidrug Resistance Gene MDR1 (ABCB1)

2004

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The multidrug resistance (MDR1) gene product P-glycoprotein is a membrane protein that functions as an ATP-dependent efflux pump, transporting exogenous and endogenous substrates from the inside of cells to the outside. Physiological expression of P-glycoprotein in tissues with excretory or protective function is a major determinant of drug disposition and provides a cellular defense mechanism against potentially harmful compounds. Therefore, P-glycoprotein has significant impact on therapeutic efficacy and toxicity as it plays a key role in absorption of oral medications from the intestinal tract, excretion into bile and urine, and distribution into protected tissues such as the brain and testes. There is increasing interest in the possible role of genetic variation in MDR1 in drug therapy. Numerous genetic polymorphisms in MDR1 have been described, some of which have been shown to determine Pglycoprotein expression levels and substrate transport. Furthermore, some of these polymorphisms have an impact on pharmacokinetic and pharmacodynamic profiles of drug substrates and directly influence outcome and prognosis of certain diseases. This review will focus on the impact of genetic variation in MDR1 on expression and function of P-glycoprotein and the implications of this variation for drug therapy and disease risk.

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“…The ABCB1 1199G4A SNP was observed with low frequency, but it was comparable to what has been observed in the literature. 13,15,16 We observed all three alleles at the 2677 locus; however, the 2677A allele was found with low prevalence and was only observed in heterozygous patients 2677TA or 2677GA.…”

Section: Genotype Frequenciesmentioning

confidence: 61%

Pharmacogenomic associations in ABCB1 and CYP3A5 with acute kidney injury and chronic kidney disease after myeloablative hematopoietic cell transplantation

et al. 2007

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Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects

Abstract: 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.

Cited by 672 publications

References 20 publications

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

Functional Implications of Genetic Polymorphisms in the Multidrug Resistance Gene MDR1 (ABCB1)

Pharmacogenomic associations in ABCB1 and CYP3A5 with acute kidney injury and chronic kidney disease after myeloablative hematopoietic cell transplantation

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