Donor ABCB1 variant associates with increased risk for kidney allograft failure

Research output: Contribution to journalArticlepeer-review

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Donor ABCB1 variant associates with increased risk for kidney allograft failure. / Moore, Jason; McKnight, Amy Jayne; Döhler, Bernd; Simmonds, Matthew J; Courtney, Aisling E; Brand, Oliver J; Briggs, David; Ball, Simon; Cockwell, Paul; Patterson, Christopher C; Maxwell, Alexander P; Gough, Stephen C L; Opelz, Gerhard; Borrows, Richard.

In: Journal of the American Society of Nephrology, Vol. 23, No. 11, 11.2012, p. 1891-9.

Research output: Contribution to journalArticlepeer-review

Harvard

Moore, J, McKnight, AJ, Döhler, B, Simmonds, MJ, Courtney, AE, Brand, OJ, Briggs, D, Ball, S, Cockwell, P, Patterson, CC, Maxwell, AP, Gough, SCL, Opelz, G & Borrows, R 2012, 'Donor ABCB1 variant associates with increased risk for kidney allograft failure', Journal of the American Society of Nephrology, vol. 23, no. 11, pp. 1891-9. https://doi.org/10.1681/ASN.2012030260

APA

Moore, J., McKnight, A. J., Döhler, B., Simmonds, M. J., Courtney, A. E., Brand, O. J., Briggs, D., Ball, S., Cockwell, P., Patterson, C. C., Maxwell, A. P., Gough, S. C. L., Opelz, G., & Borrows, R. (2012). Donor ABCB1 variant associates with increased risk for kidney allograft failure. Journal of the American Society of Nephrology, 23(11), 1891-9. https://doi.org/10.1681/ASN.2012030260

Vancouver

Author

Moore, Jason ; McKnight, Amy Jayne ; Döhler, Bernd ; Simmonds, Matthew J ; Courtney, Aisling E ; Brand, Oliver J ; Briggs, David ; Ball, Simon ; Cockwell, Paul ; Patterson, Christopher C ; Maxwell, Alexander P ; Gough, Stephen C L ; Opelz, Gerhard ; Borrows, Richard. / Donor ABCB1 variant associates with increased risk for kidney allograft failure. In: Journal of the American Society of Nephrology. 2012 ; Vol. 23, No. 11. pp. 1891-9.

Bibtex

@article{da12253962ac439ba000b93ce3bca1a9,
title = "Donor ABCB1 variant associates with increased risk for kidney allograft failure",
abstract = "The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.",
keywords = "Polymorphism, Single Nucleotide, Kidney Transplantation, Humans, Calcineurin, Genetic Association Studies, Receptors, Steroid, Linkage Disequilibrium, Great Britain, Tissue Donors, Cyclophilins, Kaplan-Meier Estimate, P-Glycoprotein, Cytochrome P-450 CYP3A, Risk Factors, Graft Survival, Adult, Cohort Studies, Middle Aged, Male, Female",
author = "Jason Moore and McKnight, {Amy Jayne} and Bernd D{\"o}hler and Simmonds, {Matthew J} and Courtney, {Aisling E} and Brand, {Oliver J} and David Briggs and Simon Ball and Paul Cockwell and Patterson, {Christopher C} and Maxwell, {Alexander P} and Gough, {Stephen C L} and Gerhard Opelz and Richard Borrows",
year = "2012",
month = nov,
doi = "10.1681/ASN.2012030260",
language = "English",
volume = "23",
pages = "1891--9",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",

}

RIS

TY - JOUR

T1 - Donor ABCB1 variant associates with increased risk for kidney allograft failure

AU - Moore, Jason

AU - McKnight, Amy Jayne

AU - Döhler, Bernd

AU - Simmonds, Matthew J

AU - Courtney, Aisling E

AU - Brand, Oliver J

AU - Briggs, David

AU - Ball, Simon

AU - Cockwell, Paul

AU - Patterson, Christopher C

AU - Maxwell, Alexander P

AU - Gough, Stephen C L

AU - Opelz, Gerhard

AU - Borrows, Richard

PY - 2012/11

Y1 - 2012/11

N2 - The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

AB - The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

KW - Polymorphism, Single Nucleotide

KW - Kidney Transplantation

KW - Humans

KW - Calcineurin

KW - Genetic Association Studies

KW - Receptors, Steroid

KW - Linkage Disequilibrium

KW - Great Britain

KW - Tissue Donors

KW - Cyclophilins

KW - Kaplan-Meier Estimate

KW - P-Glycoprotein

KW - Cytochrome P-450 CYP3A

KW - Risk Factors

KW - Graft Survival

KW - Adult

KW - Cohort Studies

KW - Middle Aged

KW - Male

KW - Female

U2 - 10.1681/ASN.2012030260

DO - 10.1681/ASN.2012030260

M3 - Article

C2 - 23064017

VL - 23

SP - 1891

EP - 1899

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 11

ER -