Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation

• Type of Material: Article
• Authors: Jun Ma, Wake Forest University; Jasmin Divers, Wake Forest University; Nicholette D. Palmer, Wake Forest University; Bruce A. Julian, University of Alabama at Birmingham; Ajay K. Israni, University of Minnesota; David Schladt, Minneapolis Medical Research Foundation; Stephen Pastan, Emory University; Kryt Chattrabhuti, Wake Forest University; Michael D. Gautreaux, Wake Forest University; Vera Hauptfeld, University of Alabama at Birmingham; Robert Bray, Emory University; Allan Kirk, Emory University; W. Mark Brown, Wake Forest University; Robert S. Gaston, University of Alabama at Birmingham; Jeffrey Rogers, Wake Forest University; Alan C. Farney, Wake Forest University; Giuseppe Orlando, Wake Forest University; Robert J. Stratta, Wake Forest University; Meijian Guan, Wake Forest University; Amudha Palanisamy, Wake Forest University; Amber M. Reeves-Daniel, Wake Forest University; Donald W. Bowden, Wake Forest University; Carl D. Langefeld, Wake Forest University; Pamela J. Hicks, Wake Forest University; Lijun Ma, Wake Forest University; Barry I. Freedman, Wake Forest University
• Language: English
• Date: 2015-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 International Society of Nephrology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ki.2015.105
• Title of Journal or Parent Work: Kidney International
• ISSN: 0085-2538
• Volume: 88
• Issue: 3
• Start Page: 584
• End Page: 592
• Grant/Funding Information: This project was supported in part by NIH RO1 MD009055 (JD, BIF); RO1 DK07094 (BIF); RO1 NIH RO1 DK084149 (BIF); and NIH/NIAD Genomics of Transplantation 5U19-AI070119 (AKI).; This work has also been made possible through an International Society of Nephrology Fellowship and Shanghai Jiaotong University K.C. Wong Medical Fellowship Fund (Jun Ma).
• Keywords: Life Sciences & Biomedicine; POLYMORPHISM; ASSOCIATION; NEPHROTOXICITY; APOL1; CALCINEURIN INHIBITOR; GENOTYPE; RISK; Urology & Nephrology; P-GLYCOPROTEIN; ABCB1; EXPRESSION; African American; RENAL-FUNCTION; kidney transplantation; Science & Technology; CAV1; allograft failure; AFRICAN-AMERICANS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology

Abstract

Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 European American (EA) deceased donors based on 38 single-nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1, including previously associated index and haplotype-tagging SNPs. Tests for association with time to allograft failure were performed for the 1233 resultant kidney transplantations, adjusting for recipient age, sex, ethnicity, cold ischemia time, panel reactive antibody, human leukocyte antigen match, expanded-criteria donation, and APOL1-nephropathy variants in AA donors. Interaction analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of all transplantations, ABCB1 index SNP rs1045642 was associated with time to allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1 SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors. Interactions between ABCB1 and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from AA donors.