Association of four DNA polymorphisms with acute rejection after kidney transplantation

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.

Vanrenterghem, Yves (author)
Nashan, Bjoern (author)
Vincenti, Flavio (author)
Ekberg, HenrikLund University,Lunds universitet,Enheten för forskning kring njurfunktion och njursjukdom,Kirurgi,Forskargrupper vid Lunds universitet,Renal Research Unit,Surgery,Lund University Research Groups(Swepub:lu)kir-hek (author)
Lindpaintner, Klaus (author)
Rashford, Michelle (author)
Nasmyth-Miller, Clare (author)
Voulgari, Athina (author)
Spleiss, Olivia (author)
Truman, Matthew (author)
Essioux, Laurent (author)
Enheten för forskning kring njurfunktion och njursjukdomKirurgi (creator_code:org_t)

In:Transplant International: Frontiers Media SA21:9, s. 879-8911432-22770934-0874

By the author/editor: Grinyo, Josep; Vanrenterghem, Y ...; Nashan, Bjoern; Vincenti, Flavio; Ekberg, Henrik; Lindpaintner, Kl ...; show more...; Rashford, Michel ...; Nasmyth-Miller, ...; Voulgari, Athina; Spleiss, Olivia; Truman, Matthew; Essioux, Laurent; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Surgery

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