ABCC2 p.Tyr39Phe
| Predicted by SNAP2: | A: D (80%), C: D (80%), D: D (95%), E: D (95%), F: N (53%), G: D (85%), H: D (91%), I: D (80%), K: D (95%), L: D (80%), M: D (91%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (85%), T: D (91%), V: D (75%), W: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, 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, |
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[hide] Interindividual variability in hepatic expression ... Drug Metab Dispos. 2012 May;40(5):852-5. Epub 2012 Feb 8. Deo AK, Prasad B, Balogh L, Lai Y, Unadkat JD
Interindividual variability in hepatic expression of the multidrug resistance-associated protein 2 (MRP2/ABCC2): quantification by liquid chromatography/tandem mass spectrometry.
Drug Metab Dispos. 2012 May;40(5):852-5. Epub 2012 Feb 8., [PMID:22318656]
Abstract [show]
Multidrug-associated protein 2 (MRP2) is an efflux transporter that is expressed at the bile canalicular membrane. To allow in vitro to in vivo extrapolation of the contribution of MRP2 toward hepatic disposition of its substrates, data on the interindividual variability of hepatic MRP2 protein expression are required. Therefore, we quantified the expression of MRP2 in the University of Washington (UW) human liver bank (n = 51) using a modified version of a previously validated liquid chromatography/tandem mass spectrometry assay. An unlabeled (LTIIPQDPILFSGSLR) and stable isotope-labeled (LTIIPQDPILFSGSL[(13)C(6)(15)N(1)]R) surrogate peptide for MRP2 were used as the calibrator and internal standard, respectively. After isolation of the membrane fraction from the liver tissue, in-solution tryptic digestion was conducted. Quality control samples created by spiking human serum albumin or pooled human liver (n = 51) matrix with three different MRP2 synthetic peptide concentrations generated error and precision values of less than 15%. As determined by the surrogate peptide, the average MRP2 expression in the UW liver bank samples was 1.54 +/- 0.64 fmol/mug liver membrane protein and was found to be independent of age (7-63 years) or sex. A single nucleotide polymorphism in the promoter region (rs717620), previously thought to affect MRP2 expression, did not influence hepatic expression of MRP2. In contrast, the single nucleotide polymorphism 21214G>A (V417I; rs2273697) was associated with significantly higher hepatic MRP2 expression.
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No. Sentence Comment
85 Genotyping revealed polymorphisms for ABCC2 at the following sites: 1846AϾT(Y39F; rs927344), 21214GϾA(V417I; rs2273697), -24CϾT (rs717620), 36351TϾG(L849R; rs45494393), 53395TϾA(V1188E; rs17222723), 61606CϾT(I1324I; rs3740066), SNP-1 - - + - - - + - - + - - + - - - - - + - - - - - + - - + - - - - - - - - - + + - - + - - - - - - + + - SNP-2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - + - - - - - - - - - - - + - - - - - - - - + - SNP-3 - - - + + - - - - - - - - + + + - - + + - - + + - - - - - - + - - + + + - + - + - - - + - - - + + - - 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 HL102 HL103 HL105 HL106 HL111 HL112 HL113 HL114 HL115 HL119 HL127 HL129 HL132 HL137 HL139 HL152 HL155 HL157 HL167 HL168 HL171 HL172 Average HL104 HL109 HL120 HL126 HL128 HL133 HL135 HL142 HL144 HL150 HL151 HL153 HL156 HL158 HL159 HL162 HL163 HL165 Average HL125 HL136 HL138 HL146 Average HL143 HL145 HL147 HL149 HL166 Average HL141 HL140 MRP2protein(fmol/ugprotein) A Acute injury FaƩy FibroƟc Normal B FIG. 2.
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ABCC2 p.Tyr39Phe 22318656:85:82
status: NEW