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

Jun Ma; Jasmin Divers; Nicholette D. Palmer; Bruce A. Julian; Ajay K. Israni; David Schladt; Stephen O. Pastan; Kryt Chattrabhuti; Michael D. Gautreaux; Vera Hauptfeld; Robert A. Bray; Allan D. Kirk; W. Mark Brown; Robert S. Gaston; Jeffrey Rogers; Alan C. Farney; Giuseppe Orlando; Robert J. Stratta; Meijian Guan; Amudha Palanisamy; Amber M. Reeves-Daniel; Donald W. Bowden; Carl D. Langefeld; Pamela J. Hicks; Lijun Ma; Barry I. Freedman

doi:10.1038/ki.2015.105

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

Jun Ma, Jasmin Divers, Nicholette D. Palmer, Bruce A. Julian, Ajay K. Israni, David Schladt, Stephen O. Pastan, Kryt Chattrabhuti, Michael D. Gautreaux, Vera Hauptfeld, Robert A. Bray, Allan D. Kirk, W. Mark Brown, Robert S. Gaston, Jeffrey Rogers, Alan C. Farney, Giuseppe Orlando, Robert J. Stratta, Meijian Guan, Amudha PalanisamyAmber M. Reeves-Daniel, Donald W. Bowden, Carl D. Langefeld, Pamela J. Hicks, Lijun Ma, Barry I. Freedman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English
Pages (from-to)	584-592
Number of pages	9
Journal	Kidney International
Volume	88
Issue number	3
DOIs	https://doi.org/10.1038/ki.2015.105
State	Published - 3 Sep 2015
Externally published	Yes

Keywords

ABCB1
APOL1
African American
CAV1
allograft failure
kidney transplantation

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10.1038/ki.2015.105

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Ma, J., Divers, J., Palmer, N. D., Julian, B. A., Israni, A. K., Schladt, D., Pastan, S. O., Chattrabhuti, K., Gautreaux, M. D., Hauptfeld, V., Bray, R. A., Kirk, A. D., Brown, W. M., Gaston, R. S., Rogers, J., Farney, A. C., Orlando, G., Stratta, R. J., Guan, M., ... Freedman, B. I. (2015). Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation. Kidney International, 88(3), 584-592. https://doi.org/10.1038/ki.2015.105

@article{b55fd3d245c94a0191f6d48f55343f4c,

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.",

keywords = "ABCB1, APOL1, African American, CAV1, allograft failure, kidney transplantation",

author = "Jun Ma and Jasmin Divers and Palmer, {Nicholette D.} and Julian, {Bruce A.} and Israni, {Ajay K.} and David Schladt and Pastan, {Stephen O.} and Kryt Chattrabhuti and Gautreaux, {Michael D.} and Vera Hauptfeld and Bray, {Robert A.} and Kirk, {Allan D.} and Brown, {W. Mark} and Gaston, {Robert S.} and Jeffrey Rogers and Farney, {Alan C.} and Giuseppe Orlando and Stratta, {Robert J.} and Meijian Guan and Amudha Palanisamy and Reeves-Daniel, {Amber M.} and Bowden, {Donald W.} and Langefeld, {Carl D.} and Hicks, {Pamela J.} and Lijun Ma and Freedman, {Barry I.}",

note = "Publisher Copyright: {\textcopyright} 2015 International Society of Nephrology.",

year = "2015",

month = sep,

day = "3",

doi = "10.1038/ki.2015.105",

language = "English",

volume = "88",

pages = "584--592",

journal = "Kidney International",

issn = "0085-2538",

number = "3",

}

Ma, J, Divers, J, Palmer, ND, Julian, BA, Israni, AK, Schladt, D, Pastan, SO, Chattrabhuti, K, Gautreaux, MD, Hauptfeld, V, Bray, RA, Kirk, AD, Brown, WM, Gaston, RS, Rogers, J, Farney, AC, Orlando, G, Stratta, RJ, Guan, M, Palanisamy, A, Reeves-Daniel, AM, Bowden, DW, Langefeld, CD, Hicks, PJ, Ma, L & Freedman, BI 2015, 'Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation', Kidney International, vol. 88, no. 3, pp. 584-592. https://doi.org/10.1038/ki.2015.105

TY - JOUR

T1 - Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation

AU - Ma, Jun

AU - Divers, Jasmin

AU - Palmer, Nicholette D.

AU - Julian, Bruce A.

AU - Israni, Ajay K.

AU - Schladt, David

AU - Pastan, Stephen O.

AU - Chattrabhuti, Kryt

AU - Gautreaux, Michael D.

AU - Hauptfeld, Vera

AU - Bray, Robert A.

AU - Kirk, Allan D.

AU - Brown, W. Mark

AU - Gaston, Robert S.

AU - Rogers, Jeffrey

AU - Farney, Alan C.

AU - Orlando, Giuseppe

AU - Stratta, Robert J.

AU - Guan, Meijian

AU - Palanisamy, Amudha

AU - Reeves-Daniel, Amber M.

AU - Bowden, Donald W.

AU - Langefeld, Carl D.

AU - Hicks, Pamela J.

AU - Ma, Lijun

AU - Freedman, Barry I.

PY - 2015/9/3

Y1 - 2015/9/3

N2 - 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.

AB - 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.

KW - ABCB1

KW - APOL1

KW - African American

KW - CAV1

KW - allograft failure

KW - kidney transplantation

UR - http://www.scopus.com/inward/record.url?scp=84940792875&partnerID=8YFLogxK

U2 - 10.1038/ki.2015.105

DO - 10.1038/ki.2015.105

M3 - Article

C2 - 25853335

AN - SCOPUS:84940792875

SN - 0085-2538

VL - 88

SP - 584

EP - 592

JO - Kidney International

JF - Kidney International

IS - 3

ER -

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

Abstract

Keywords

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