Association of CYP3A variants with kidney transplant outcomes

C Traynor; P Conlon; PJ Phelan; P O'Kelly; Laure Elens; M McCormack; G Cavalleri; H Comber; Ron van Schaik; PJ Conlon

doi:10.3109/0886022X.2015.1007013

Association of CYP3A variants with kidney transplant outcomes

C Traynor, P Conlon, PJ Phelan, P O'Kelly, Laure Elens, M McCormack, G Cavalleri, H Comber, Ron van Schaik, PJ Conlon

Clinical Chemistry

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

9 Citations (Scopus)

Abstract

Cyclosporine is used extensively in kidney transplantation and is a substrate for cytochrome P450 enzymes. The role of cytochrome p450 polymorphisms in kidney transplant outcome has not yet been fully elucidated. We investigate the clinical impact of single nucleotide polymorphisms in CYP3A4, CYP3A5, PPAR alpha, and POR*28 in 255 kidney transplant recipients. We examine for any association with graft survival, time to first cancer, and delayed graft function, and also measure cyclosporine levels at days 3, 10, and months 1, 3, 6, and 12 after transplantation. The CYP3A4*22 allele is significant associated with the development of cancer post-kidney transplantation (HR 0.20, 95% CI 0.07-0.57, p = 0.003). It is not significantly associated with graft survival. No other SNP's were associated with graft survival time to first cancer, or delayed graft function. There was a non-significant trend of lower cyclosporine dose requirement in CYP3A4*22 carriers. Independent replication of our findings is now warranted to confirm or reject the role of CYP3A variants in cancer development following kidney transplantation.

Original language	Undefined/Unknown
Pages (from-to)	562-566
Number of pages	5
Journal	Renal Failure
Volume	37
Issue number	4
DOIs	https://doi.org/10.3109/0886022X.2015.1007013
Publication status	Published - 2015

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10.3109/0886022X.2015.1007013

Cite this

@article{9ed4656eb957499a913be050644d1665,

title = "Association of CYP3A variants with kidney transplant outcomes",

abstract = "Cyclosporine is used extensively in kidney transplantation and is a substrate for cytochrome P450 enzymes. The role of cytochrome p450 polymorphisms in kidney transplant outcome has not yet been fully elucidated. We investigate the clinical impact of single nucleotide polymorphisms in CYP3A4, CYP3A5, PPAR alpha, and POR*28 in 255 kidney transplant recipients. We examine for any association with graft survival, time to first cancer, and delayed graft function, and also measure cyclosporine levels at days 3, 10, and months 1, 3, 6, and 12 after transplantation. The CYP3A4*22 allele is significant associated with the development of cancer post-kidney transplantation (HR 0.20, 95% CI 0.07-0.57, p = 0.003). It is not significantly associated with graft survival. No other SNP's were associated with graft survival time to first cancer, or delayed graft function. There was a non-significant trend of lower cyclosporine dose requirement in CYP3A4*22 carriers. Independent replication of our findings is now warranted to confirm or reject the role of CYP3A variants in cancer development following kidney transplantation.",

author = "C Traynor and P Conlon and PJ Phelan and P O'Kelly and Laure Elens and M McCormack and G Cavalleri and H Comber and {van Schaik}, Ron and PJ Conlon",

year = "2015",

doi = "10.3109/0886022X.2015.1007013",

language = "Undefined/Unknown",

volume = "37",

pages = "562--566",

journal = "Renal Failure",

issn = "0886-022X",

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number = "4",

}

TY - JOUR

T1 - Association of CYP3A variants with kidney transplant outcomes

AU - Traynor, C

AU - Conlon, P

AU - Phelan, PJ

AU - O'Kelly, P

AU - Elens, Laure

AU - McCormack, M

AU - Cavalleri, G

AU - Comber, H

AU - van Schaik, Ron

AU - Conlon, PJ

PY - 2015

Y1 - 2015

N2 - Cyclosporine is used extensively in kidney transplantation and is a substrate for cytochrome P450 enzymes. The role of cytochrome p450 polymorphisms in kidney transplant outcome has not yet been fully elucidated. We investigate the clinical impact of single nucleotide polymorphisms in CYP3A4, CYP3A5, PPAR alpha, and POR*28 in 255 kidney transplant recipients. We examine for any association with graft survival, time to first cancer, and delayed graft function, and also measure cyclosporine levels at days 3, 10, and months 1, 3, 6, and 12 after transplantation. The CYP3A4*22 allele is significant associated with the development of cancer post-kidney transplantation (HR 0.20, 95% CI 0.07-0.57, p = 0.003). It is not significantly associated with graft survival. No other SNP's were associated with graft survival time to first cancer, or delayed graft function. There was a non-significant trend of lower cyclosporine dose requirement in CYP3A4*22 carriers. Independent replication of our findings is now warranted to confirm or reject the role of CYP3A variants in cancer development following kidney transplantation.

AB - Cyclosporine is used extensively in kidney transplantation and is a substrate for cytochrome P450 enzymes. The role of cytochrome p450 polymorphisms in kidney transplant outcome has not yet been fully elucidated. We investigate the clinical impact of single nucleotide polymorphisms in CYP3A4, CYP3A5, PPAR alpha, and POR*28 in 255 kidney transplant recipients. We examine for any association with graft survival, time to first cancer, and delayed graft function, and also measure cyclosporine levels at days 3, 10, and months 1, 3, 6, and 12 after transplantation. The CYP3A4*22 allele is significant associated with the development of cancer post-kidney transplantation (HR 0.20, 95% CI 0.07-0.57, p = 0.003). It is not significantly associated with graft survival. No other SNP's were associated with graft survival time to first cancer, or delayed graft function. There was a non-significant trend of lower cyclosporine dose requirement in CYP3A4*22 carriers. Independent replication of our findings is now warranted to confirm or reject the role of CYP3A variants in cancer development following kidney transplantation.

U2 - 10.3109/0886022X.2015.1007013

DO - 10.3109/0886022X.2015.1007013

M3 - Article

C2 - 25644970

SN - 0886-022X

VL - 37

SP - 562

EP - 566

JO - Renal Failure

JF - Renal Failure

IS - 4

ER -