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Title: Association of four DNA polymorphisms with acute rejection after kidney transplantation
Authors: Grinyo, Josep ×
Vanrenterghem, Yves
Nashan, Bjoern
Vincenti, Flavio
Ekberg, Henrik
Lindpaintner, Klaus
Rashford, Michelle
Nasmyth-Miller, Clare
Voulgari, Athina
Spleiss, Olivia
Truman, Matthew
Essioux, Laurent #
Issue Date: Sep-2008
Publisher: Blackwell publishing
Series Title: Transplant international vol:21 issue:9 pages: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 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.
ISSN: 0934-0874
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Nephrology
× corresponding author
# (joint) last author

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