Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Baan, C.C. et al.

Baan, Balk, Holweg, van Riemsdijk, Maat, Vantrimpont, Niesters, Weimar,

Renal failure after clinical heart transplantation is associated with the TGF-beta 1 codon 10 gene polymorphism.

BACKGROUND: To determine whether genetic factors are involved in the development of renal dysfunction due to cyclosporine nephrotoxicity, we analyzed 2 polymorphisms in the signal sequence of the transforming growth factor (TGF)-beta 1 gene; codon 10 (Leu(10) --> Pro) and codon 25 (Arg(25) --> Pro). METHOD: Using sequence specific oligonucleotide probing, we analyzed both TGF-beta1 gene polymorphisms in cardiac allograft recipients (n = 168) who survived at least 1 year with minimal follow-up of 7 years. Patients received cyclosporine and steroids as maintenance immunosuppressive therapy. Renal dysfunction was defined as a serum creatinine > or = 250 micromol/liter. RESULTS: Renal dysfunction was observed in 2% (3/168) of the patients at 1 year, in 7% (11/160) at 3 years, in 12% (18/152) at 5 years, and in 20% (26/131) at 7 years post-transplantation. The genotypic distributions for TGF-beta1 codon 10 were 7% Pro/Pro, 61% Pro/Leu, and 32% Leu/Leu, and for codon 25 these percentages were 1% Pro/Pro, 12% Pro/Arg, and 87% Arg/Arg. We found an association between the TGF-beta 1 genotype encoding proline at codon 10 and renal dysfunction. At 7 years post-transplantation, 26% (23/89) of the patients with the heterozygous Pro/Leu or homozygous Pro/Pro genotype had renal dysfunction vs only 7% (3/42) of the patients with the homozygous Leu/Leu genotype (p = 0.017). For the TGF-beta1 codon 25 genotypes, we found no association between TGF-beta 1 genotypes and renal dysfunction. CONCLUSION: Our data support the hypothesis that TGF-beta 1 is involved in the process leading to renal insufficiency in cyclosporine-treated cardiac allograft recipients. In these patients the presence of TGF-beta 1 Pro(10) might be a risk factor.[1]

References

Renal failure after clinical heart transplantation is associated with the TGF-beta 1 codon 10 gene polymorphism. Baan, C.C., Balk, A.H., Holweg, C.T., van Riemsdijk, I.C., Maat, L.P., Vantrimpont, P.J., Niesters, H.G., Weimar, W. J. Heart Lung Transplant. (2000) [Pubmed]

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