title: Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.
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.
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Jun
authors: J
authors: Ma
authors: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Jasmin
authors: J
authors: Divers
authors: Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Nicholette D
authors: ND
authors: Palmer
authors: Department of Medicine, Division of Nephrology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
authors: Bruce A
authors: BA
authors: Julian
authors: Department of Medicine, Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota, USA.|Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA.
authors: Ajay K
authors: AK
authors: Israni
authors: Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA.
authors: David
authors: D
authors: Schladt
authors: Department of Medicine, Renal Division, Emory University School of Medicine, Atlanta, Georgia, USA.
authors: Stephen O
authors: SO
authors: Pastan
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Kryt
authors: K
authors: Chattrabhuti
authors: General Surgery & HLA Immunogenetics Lab, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Michael D
authors: MD
authors: Gautreaux
authors: Alabama Regional Histocompatibility Laboratory at UAB, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
authors: Vera
authors: V
authors: Hauptfeld
authors: Department of Pathology & Lab Medicine; Emory School of Medicine, Atlanta, Georgia, USA.
authors: Robert A
authors: RA
authors: Bray
authors: Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
authors: Allan D
authors: AD
authors: Kirk
authors: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: W Mark
authors: WM
authors: Brown
authors: Department of Medicine, Division of Nephrology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
authors: Robert S
authors: RS
authors: Gaston
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Jeffrey
authors: J
authors: Rogers
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Alan C
authors: AC
authors: Farney
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Giuseppe
authors: G
authors: Orlando
authors: Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Robert J
authors: RJ
authors: Stratta
authors: Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Meijian
authors: M
authors: Guan
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Amudha
authors: A
authors: Palanisamy
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Amber M
authors: AM
authors: Reeves-Daniel
authors: Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Donald W
authors: DW
authors: Bowden
authors: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Carl D
authors: CD
authors: Langefeld
authors: Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Pamela J
authors: PJ
authors: Hicks
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Lijun
authors: L
authors: Ma
authors: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Center for Genomics & Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors: Barry I
authors: BI
authors: Freedman
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics; D064591:Allografts; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics; D051242:Caveolin 1 / Q000235:genetics*; D046148:Donor Selection; D005260:Female; D056726:Genetic Association Studies; D006085:Graft Survival / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects; D008075:Lipoproteins, HDL / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome; D014481:United States; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; C108666:APOL1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; C495540:CAV1 protein, human; D051242:Caveolin 1; D008075:Lipoproteins, HDL