ABCMdb

PMID: 17178267

Crettol S, Deglon JJ, Besson J, Croquette-Krokar M, Hammig R, Gothuey I, Monnat M, Eap CB
ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment.
Clin Pharmacol Ther. 2006 Dec;80(6):668-81., [PubMed]

Sentences

No. Mutations Sentence Comment

24 ABCB1 p.Asn21Asp P-gp is expressed in various human tissues, including the intestine, liver, kidneys, testes, lymphocytes, and blood-brain barrier.21 P-gp actively transports xenobiotics from the intracellular to the extracellular domain, resulting in a protective role against their potentially toxic accumulation, by enhancement of their elimination and limitation of their distribution in the body.22 The important role of P-gp in the limitation of access of xenobiotics to the brain has been demonstrated in vivo by studies on P-gp-deficient mice.23 The synonymous 3435CϾT single-nucleotide polymorphism (SNP) of the ABCB1 gene has been associated with lower P-gp expression.24 Since this first report by Hoffmeyer et al,24 contradictory results have been published on the impact of various ABCB1 SNPs (mostly 3435CϾT and 2677GϾT) on P-gp expression and function and on the kinetics of different P-gp substrates.21,25 Interestingly, it has recently been shown that the 3435TT genotype, in linkage disequilibrium with the 2677TT genotype, is associated with reduced P-gp expression resulting from a decrease in messenger ribonucleic acid stability.26 Another interesting SNP, ABCB1 61AϾG (N21D), is a nonsynonymous polymorphism. Login to comment