ABCMdb

PMID: 17700595

Woodahl EL, Hingorani SR, Wang J, Guthrie KA, McDonald GB, Batchelder A, Li M, Schoch HG, McCune JS
Pharmacogenomic associations in ABCB1 and CYP3A5 with acute kidney injury and chronic kidney disease after myeloablative hematopoietic cell transplantation.
Pharmacogenomics J. 2008 Aug;8(4):248-55. Epub 2007 Aug 14., [PubMed]

Sentences

No. Mutations Sentence Comment

22 ABCB1 p.Ser400Asn ABCB1 p.Ser400Asn We also evaluated two nonsynonymous SNPs; the tri-allelic non-synonymous SNP at nucleotide position 2677, which results in a 2677G4T (Ala893Ser) or a 2677G4A (Ala893Thr) transition, and the 1199G4A SNP (Ser400Asn) that we have shown to cause a functional alteration in P-gp activity.10,11 Because significant linkage disequilibrium (LD) exists in ABCB1, we also evaluated the associated risk of ABCB1 haplotypes.12-14 Understanding the influence of genetic variability in the intrarenal concentrations of CNIs in post-HCT patients may allow for the a priori identification of patients at high risk of CNI-induced renal dysfunction who would be candidates for non-CNI containing regimens. Login to comment 71 ABCB1 p.Ser400Asn ABCB1 is highly polymorphic and displays considerable LD and several SNPs have been associated with changes in the expression and activity of P-gp.9 The first ABCB1 polymorphism found to be associated with alterations in P-gp was the synonymous SNP 3435C4T.16 Subsequently, it was reported that 3435C4T is in LD with two other ABCB1 SNPs; a tri-allelic non-synonymous SNP at nucleotide position 2677, which results in a 2677G4T (Ala893Ser) and a 2677G4A (Ala893Thr) transition, as well as 1236C4T, another synonymous SNP.13 In addition, we have recently observed a functional alteration in P-gp activity due to another non-synonymous ABCB1 polymorphism, 1199G4A (Ser400Asn).10,11 The in vivo significance of ABCB1 polymorphisms has been conflicting as to their functional effect on renal P-gp expression.22-24 Since significant linkage exists in the ABCB1 gene, it is important to understand the role of ABCB1 haplotypes in pharmacogenomic association studies. Login to comment