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Association of four DNA polymorphisms with acute rejection after kidney transplantation

Grinyo, Josep; Vanrenterghem, Yves; Nashan, Bjoern; Vincenti, Flavio; Ekberg, Henrik LU ; Lindpaintner, Klaus; Rashford, Michelle; Nasmyth-Miller, Clare; Voulgari, Athina and Spleiss, Olivia, et al. (2008) In Transplant International 21(9). p.879-891
Abstract
Renal transplant outcomes exhibit large inter-individual variability, possibly on account of genetic variation in immune-response mediators and genes influencing the pharmacodynamics/pharmacokinetics of immunosuppressants. We examined 21 polymorphisms from 10 genes in 237 de novo renal transplant recipients participating in an open-label, multicenter study [Cyclosporine Avoidance Eliminates Serious Adverse Renal-toxicity (CAESAR)] investigating renal function and biopsy-proven acute rejection (BPAR) with different cyclosporine A regimens and mycophenolate mofetil. Genes were selected for their immune response and pharmacodynamic/pharmacokinetic relevance and were tested for association with BPAR. Four polymorphisms were significantly... (More)
Renal transplant outcomes exhibit large inter-individual variability, possibly on account of genetic variation in immune-response mediators and genes influencing the pharmacodynamics/pharmacokinetics of immunosuppressants. We examined 21 polymorphisms from 10 genes in 237 de novo renal transplant recipients participating in an open-label, multicenter study [Cyclosporine Avoidance Eliminates Serious Adverse Renal-toxicity (CAESAR)] investigating renal function and biopsy-proven acute rejection (BPAR) with different cyclosporine A regimens and mycophenolate mofetil. Genes were selected for their immune response and pharmacodynamic/pharmacokinetic relevance and were tested for association with BPAR. Four polymorphisms were significantly associated with BPAR. The ABCB1 2677T allele tripled the odds of developing BPAR (OR: 3.16, 95% CI [1.50-6.67]; P = 0.003), as did the presence of at least one IMPDH2 3757C allele (OR: 3.39, 95% CI [1.42-8.09]; P = 0.006). BPAR was almost fivefold more likely in patients homozygous for IL-10 -592A (OR: 4.71, 95% CI [1.52-14.55]; P = 0.007) and twice as likely in patients with at least one A allele of TNF-alpha G-308A (OR: 2.18, 95% CI [1.08-4.41]; P = 0.029). There were no statistically significant interactions between polymorphisms, or the different treatment regimens. Variation in genes of immune response and pharmacodynamic/pharmacokinetic relevance may be important in understanding acute rejection after renal transplant. (Less)
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Contribution to journal
publication status
published
subject
keywords
single nucleotide polymorphism, acute rejection, kidney transplantation
in
Transplant International
volume
21
issue
9
pages
879 - 891
publisher
Springer
external identifiers
  • wos:000258381400008
  • scopus:49649106273
ISSN
1432-2277
DOI
10.1111/j.1432-2277.2008.00679.x
language
English
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yes
id
397dfefb-233d-4281-98d3-dc5d7845ab51 (old id 1252116)
date added to LUP
2008-11-10 16:08:54
date last changed
2017-06-11 04:04:33
@article{397dfefb-233d-4281-98d3-dc5d7845ab51,
  abstract     = {Renal transplant outcomes exhibit large inter-individual variability, possibly on account of genetic variation in immune-response mediators and genes influencing the pharmacodynamics/pharmacokinetics of immunosuppressants. We examined 21 polymorphisms from 10 genes in 237 de novo renal transplant recipients participating in an open-label, multicenter study [Cyclosporine Avoidance Eliminates Serious Adverse Renal-toxicity (CAESAR)] investigating renal function and biopsy-proven acute rejection (BPAR) with different cyclosporine A regimens and mycophenolate mofetil. Genes were selected for their immune response and pharmacodynamic/pharmacokinetic relevance and were tested for association with BPAR. Four polymorphisms were significantly associated with BPAR. The ABCB1 2677T allele tripled the odds of developing BPAR (OR: 3.16, 95% CI [1.50-6.67]; P = 0.003), as did the presence of at least one IMPDH2 3757C allele (OR: 3.39, 95% CI [1.42-8.09]; P = 0.006). BPAR was almost fivefold more likely in patients homozygous for IL-10 -592A (OR: 4.71, 95% CI [1.52-14.55]; P = 0.007) and twice as likely in patients with at least one A allele of TNF-alpha G-308A (OR: 2.18, 95% CI [1.08-4.41]; P = 0.029). There were no statistically significant interactions between polymorphisms, or the different treatment regimens. Variation in genes of immune response and pharmacodynamic/pharmacokinetic relevance may be important in understanding acute rejection after renal transplant.},
  author       = {Grinyo, Josep and Vanrenterghem, Yves and Nashan, Bjoern and Vincenti, Flavio and Ekberg, Henrik and Lindpaintner, Klaus and Rashford, Michelle and Nasmyth-Miller, Clare and Voulgari, Athina and Spleiss, Olivia and Truman, Matthew and Essioux, Laurent},
  issn         = {1432-2277},
  keyword      = {single nucleotide polymorphism,acute rejection,kidney transplantation},
  language     = {eng},
  number       = {9},
  pages        = {879--891},
  publisher    = {Springer},
  series       = {Transplant International},
  title        = {Association of four DNA polymorphisms with acute rejection after kidney transplantation},
  url          = {http://dx.doi.org/10.1111/j.1432-2277.2008.00679.x},
  volume       = {21},
  year         = {2008},
}