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

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 - Kidney Int. (2015)

Bottom Line: 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.Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

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.

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Kaplan-Meier plots with time to allograft failure based on the significant interaction (p=0.001, dominant model) between APOL1 risk variants (recessive; APOL1=2 signifies risk) and ABCB1 haplotype-tagging single nucleotide polymorphism rs956825 (rs956835=1/2 signifies risk).
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Figure 1: Kaplan-Meier plots with time to allograft failure based on the significant interaction (p=0.001, dominant model) between APOL1 risk variants (recessive; APOL1=2 signifies risk) and ABCB1 haplotype-tagging single nucleotide polymorphism rs956825 (rs956835=1/2 signifies risk).

Mentions: Table 4 displays results of testing for genetic interaction between ABCB1 and CAV1 SNPs with the powerful APOL1 G1 and G2 nephropathy-risk variants in transplantation of allografts from AA donors. The recessive model was used to define APOL1-mediated risk.13 Significant interaction effects with APOL1 were observed for ABCB1 htSNP rs956825 (p=0.001; dominant model) and CAV1 htSNP rs6466583 (p=0.004; recessive model), revealing potentially important gene-gene interactions on time to renal allograft survival (Figures 1 and 2).


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

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 - Kidney Int. (2015)

Kaplan-Meier plots with time to allograft failure based on the significant interaction (p=0.001, dominant model) between APOL1 risk variants (recessive; APOL1=2 signifies risk) and ABCB1 haplotype-tagging single nucleotide polymorphism rs956825 (rs956835=1/2 signifies risk).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556550&req=5

Figure 1: Kaplan-Meier plots with time to allograft failure based on the significant interaction (p=0.001, dominant model) between APOL1 risk variants (recessive; APOL1=2 signifies risk) and ABCB1 haplotype-tagging single nucleotide polymorphism rs956825 (rs956835=1/2 signifies risk).
Mentions: Table 4 displays results of testing for genetic interaction between ABCB1 and CAV1 SNPs with the powerful APOL1 G1 and G2 nephropathy-risk variants in transplantation of allografts from AA donors. The recessive model was used to define APOL1-mediated risk.13 Significant interaction effects with APOL1 were observed for ABCB1 htSNP rs956825 (p=0.001; dominant model) and CAV1 htSNP rs6466583 (p=0.004; recessive model), revealing potentially important gene-gene interactions on time to renal allograft survival (Figures 1 and 2).

Bottom Line: 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.Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

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.

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