Detection of Single Nucleotide Polymorphisms in the ABCG2 Gene in a Dutch Population

Bosch, Tessa M.; Kjellberg, Linda M.; Bouwers, Anja; Koeleman, Bobby P. C.; Schellens, Jan H.M.; Beijnen, Jos H.; Smits, Paul H.M.; Meijerman, Irma

doi:10.2165/00129785-200505020-00005

Cited by 50 publications

(34 citation statements)

References 9 publications

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“…Suboptimal BCRP activity may also be caused by genetic polymorphisms. In humans, BCRP activity can vary extensively due to known genetic polymorphisms (3,11,21) or due to intentional or coincidental use of drugs that inhibit BCRP (5). This might compromise riboflavin secretion into milk and increase dependence on the alternative FAD secretion pathway.…”

Section: Discussionmentioning

confidence: 99%

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B₂) into Milk

Herwaarden

Wagenaar

Merino

et al. 2007

Molecular and Cellular Biology

198

134

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The multidrug transporter breast cancer resistance protein (BCRP/ABCG2) is strongly induced in the mammary gland during pregnancy and lactation. We here demonstrate that BCRP is responsible for pumping riboflavin (vitamin B 2 ) into milk, thus supplying the young with this important nutrient. In Bcrp1 ؊/؊ mice, milk secretion of riboflavin was reduced >60-fold compared to that in wild-type mice. Yet, under laboratory conditions, Bcrp1 ؊/؊ pups showed no riboflavin deficiency due to concomitant milk secretion of its cofactor flavin adenine dinucleotide, which was not affected. Thus, two independent secretion mechanisms supply vitamin B 2 equivalents to milk. BCRP is the first active riboflavin efflux transporter identified in mammals and the first transporter shown to concentrate a vitamin into milk. BCRP activity elsewhere in the body protects against xenotoxins by reducing their absorption and mediating their excretion. Indeed, Bcrp1 activity increased excretion of riboflavin into the intestine and decreased its systemic availability in adult mice. Surprisingly, the paradoxical dual utilization of BCRP as a xenotoxin and a riboflavin pump is evolutionarily conserved among mammals as diverse as mice and humans. This study establishes the principle that an ABC transporter can transport a vitamin into milk and raises the possibility that other vitamins and nutrients are likewise secreted into milk by ABC transporters.

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Section: Discussionmentioning

confidence: 99%

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B₂) into Milk

Herwaarden

Wagenaar

Merino

et al. 2007

Molecular and Cellular Biology

198

134

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“…Schematic illustration of human ABCG2 and its nonsynonymous polymorphisms. SNP data on the polymorphisms of ABCG2 were obtained from the National Center for Biotechnology Information dbSNP database and recent publications (Honjo et al, 2002;Iida et al, 2002;Imai et al, 2002;Backstrom et al, 2003;Itoda et al, 2003;Zamber et al, 2003;de Jong et al, 2004;Mizuarai et al, 2004;Bosch et al, 2005;Kobayashi et al, 2005) Sf9 cells (1 ϫ 10 6 cells/ml) were infected with the amplified recombinant baculoviruses and cultured in EX-CELL 420 Insect serumfree medium at 27°C with gentle shaking. Three days after the infection, cells were harvested by centrifugation.…”

Section: Methodsmentioning

confidence: 99%

Functional Validation of the Genetic Polymorphisms of Human ATP-Binding Cassette (ABC) Transporter ABCG2: Identification of Alleles That Are Defective in Porphyrin Transport

Tamura¹,

Watanabe²,

Saito³

et al. 2006

Mol Pharmacol

127

103

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The ATP-binding cassette (ABC) transporter ABCG2 has been implicated to play a significant role in the response of patients to medication and/or the risk of diseases. To clarify the possible physiological or pathological relevance of ABCG2 polymorphisms, we have functionally validated single nucleotide polymorphisms (SNP) of ABCG2. In the present study, based on the currently available data on SNPs and acquired mutations, we have created a total of 18 variant forms of ABCG2 (V12M,

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“…Multiple polymorphisms in ABCG2 have been identified that may modulate the functional activity of ABCG2 [22][23][24]. Particularly relevant SNPs in ABCG2 appear to be 421CϾA (Gln141Lys) and the nonsense SNP 376CϾT (Gln126stop).…”

Section: Bcrp (Abcg2)mentioning

confidence: 99%

Part 2: Pharmacogenetic Variability in Drug Transport and Phase I Anticancer Drug Metabolism

et al. 2011

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After completing this course, the reader will be able to:1. List currently identified candidate genes involved in phase I metabolism that are potential pharmacogenetic markers in anticancer therapy.2. Describe the general effect on standard treatment of allelic variants of the candidate genes and the implications for individualized treatment.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTEquivalent drug doses in anticancer chemotherapy may lead to wide interpatient variability in drug response reflected by differences in treatment response or in severity of adverse drug reactions. Differences in the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of a drug contribute to variation in treatment outcome among patients. An important factor responsible for this variability is genetic polymorphism in genes that are involved in PK/PD processes, including drug transporters, phase I and II metabolizing enzymes, and The Oncologist CME Program is located online at http://cme.theoncologist.com/.To take the CME activity related to this article, you must be a registered user. ClinicalPharmacology:Pharmacogenetics:OpportunitiesforPatient-TailoredAnticancerTherapyThe Oncologist 2011;16:820 -834 www.TheOncologist.com by guest on May 12, 2018http://theoncologist.alphamedpress.org/ Downloaded from drug targets, and other genes that interfere with drug response. In order to achieve personalized pharmacotherapy, drug dosing and treatment selection based on genotype might help to increase treatment efficacy while reducing unnecessary toxicity. We present a series of four reviews about pharmacogenetic variability in anticancer drug treatment. This is the second review in the series and is focused on genetic variability in genes encoding drug transporters (ABCB1 and ABCG2) and phase I drug-metabolizing enzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, DPYD, CDA and BLMH) and their associations with anticancer drug treatment outcome. Based on the literature reviewed, opportunities for patient-tailored anticancer therapy are presented. The Oncologist 2011;16:820 -834

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Detection of Single Nucleotide Polymorphisms in the ABCG2 Gene in a Dutch Population

Cited by 50 publications

References 9 publications

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B₂) into Milk

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B₂) into Milk

Functional Validation of the Genetic Polymorphisms of Human ATP-Binding Cassette (ABC) Transporter ABCG2: Identification of Alleles That Are Defective in Porphyrin Transport

Part 2: Pharmacogenetic Variability in Drug Transport and Phase I Anticancer Drug Metabolism

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Detection of Single Nucleotide Polymorphisms in the ABCG2 Gene in a Dutch Population

Cited by 50 publications

References 9 publications

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B2) into Milk

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B2) into Milk

Functional Validation of the Genetic Polymorphisms of Human ATP-Binding Cassette (ABC) Transporter ABCG2: Identification of Alleles That Are Defective in Porphyrin Transport

Part 2: Pharmacogenetic Variability in Drug Transport and Phase I Anticancer Drug Metabolism

Contact Info

Product

Resources

About

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B₂) into Milk

Multidrug Transporter ABCG2/Breast Cancer Resistance Protein Secretes Riboflavin (Vitamin B₂) into Milk