ABCC2 p.Cys1446Gly
| Predicted by SNAP2: | A: N (57%), D: D (85%), E: D (85%), F: D (85%), G: D (75%), H: D (66%), I: D (80%), K: D (85%), L: D (85%), M: D (80%), N: D (75%), P: D (91%), Q: D (85%), R: D (85%), S: D (53%), T: D (63%), V: D (80%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Xenobiotic, bile acid, and cholesterol transporter... Pharmacol Rev. 2010 Mar;62(1):1-96. Epub 2010 Jan 26. Klaassen CD, Aleksunes LM
Xenobiotic, bile acid, and cholesterol transporters: function and regulation.
Pharmacol Rev. 2010 Mar;62(1):1-96. Epub 2010 Jan 26., [PMID:20103563]
Abstract [show]
Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting beta polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) alpha and beta] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of regulatory factors that influence transporter expression and function, including transcriptional activation and post-translational modifications as well as subcellular trafficking. Sex differences, ontogeny, and pharmacological and toxicological regulation of transporters are also addressed. Transporters are important transmembrane proteins that mediate the cellular entry and exit of a wide range of substrates throughout the body and thereby play important roles in human physiology, pharmacology, pathology, and toxicology.
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No. Sentence Comment
6525 Pravastatin plasma concentrations are reduced in healthy volunteers carrying the C1446G synonymous ABCC2 (MRP2) variant (Niemi et al., 2006a).
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ABCC2 p.Cys1446Gly 20103563:6525:81
status: NEW6524 Pravastatin plasma concentrations are reduced in healthy volunteers carrying the C1446G synonymous ABCC2 (MRP2) variant (Niemi et al., 2006a).
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ABCC2 p.Cys1446Gly 20103563:6524:81
status: NEW[hide] Impact of ABCC2, ABCG2 and SLCO1B1 polymorphisms o... Drug Metab Pharmacokinet. 2012 Sep 25. Oh ES, Kim CO, Cho SK, Park MS, Chung JY
Impact of ABCC2, ABCG2 and SLCO1B1 polymorphisms on the pharmacokinetics of pitavastatin in humans.
Drug Metab Pharmacokinet. 2012 Sep 25., [PMID:23007012]
Abstract [show]
Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is distributed to the liver, a target organ of action and excreted mainly into the bile. To investigate the impact of influx (OATP1B1) and efflux (MRP2, BCRP) transporter alleles on its disposition, the pharmacokinetic (PK) parameters were compared among the following groups: SLCO1B1 (*15 carrier and non-carrier), ABCC2 (G1249A, C3972T, C-24T, G1549A, and G1774T), and ABCG2 (C421A) single nucleotide polymorphisms in 45 healthy Korean volunteers. Pitavastatin AUC(last) was higher in individuals carrying the SLCO1B1*15 allele than those not carrying it (144.1+/- 55.3 vs. 84.7 +/- 25.7 hng/mL [mean +/- SD], p= 0.002). The AUC(last) varied significantly according to the ABCC2 C-24T allele (103.4 +/- 42.2, 80.2 +/- 23.8, and 39.0 hng/mL in CC, CT and TT, respectively; p= 0.027). Other SNPs of ABCC2 and ABCG2 were not significant. The effect of these transporters and body weight on the AUC(last) and C(max) were tested, and only SLCO1B1 and ABCC2 C-24T genotypes were significant factors by analysis of covariance. These variants accounted for almost 50% of the variation in AUC(last) and C(max) of pitavastatin. Therefore, ABCC2 C-24T was significantly associated with pitavastatin human PK when the known effect of SLCO1B1*15 was also considered.
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13 In heterozygotes for ABCC2 C1446G (n=3), systemic exposure and peak plasma concentration (Cmax) of pravastatin were lower than in wild-type homozygotes (CC, n=35) as a consequence of increased MRP2 mRNA expression.18) However, the variation of this allele is synonymous and has been only reported in one small Caucasian population.
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ABCC2 p.Cys1446Gly 23007012:13:27
status: NEW