PMID: 18524998

Williams JA, Andersson T, Andersson TB, Blanchard R, Behm MO, Cohen N, Edeki T, Franc M, Hillgren KM, Johnson KJ, Katz DA, Milton MN, Murray BP, Polli JW, Ricci D, Shipley LA, Vangala S, Wrighton SA
PhRMA white paper on ADME pharmacogenomics.
J Clin Pharmacol. 2008 Jul;48(7):849-89. Epub 2008 Jun 4., [PubMed]
Sentences
No. Mutations Sentence Comment
493 ABCC2 p.Arg412Gly
X
ABCC2 p.Arg412Gly 18524998:493:53
status: NEW
view ABCC2 p.Arg412Gly details
 A Dubin-Johnson patient in whom the highly conserved arginine was replaced by glycine at position 412 had unusually high methotrexate plasma concentrations and a 3-fold reduction in methotrexate elimination rate, resulting in reversible nephrotoxicity.304 A more common polymorphism in ABCC2, (27C>T), has been correlated with a 2-fold increase in exposure to methotrexate, resulting in an increased need for folate rescue in these patients.305 Although Niemi and colleagues306 indicated that there was no correlation between ABCC2 polymorphisms and pravastatin pharmacokinetics, they have recently published evidence that the 1446C>G polymorphism caused a decrease in exposure to pravastatin.307 A possible reason for the discrepancy is the low frequency of the 1446C>G genotype in the first study. Login to comment