Association of four DNA polymorphisms with acute rejection after kidney transplantation.
Transpl Int
; 21(9): 879-91, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18444945
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
/
Rejeição de Enxerto
Tipo de estudo:
Clinical_trials
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Transpl Int
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha