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A search for cyclophilin‐A gene variants in cyclosporine A‐treated renal transplanted patients
Author(s) -
MoscosoSolorzano Grace Tamara,
Ortega Francisco,
Rodríguez Isabel,
GarcíaCastro Mónica,
Gómez Ernesto,
DíazCorte Carmen,
Baltar José M.,
Alvarez Victoria,
Ortiz Alberto,
Coto Eliecer
Publication year - 2008
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2008.00867.x
Subject(s) - cypa , cyclophilin a , nephrotoxicity , medicine , genotype , single strand conformation polymorphism , exon , cyclophilin , cis trans isomerases , kidney , promoter , allele , gene , kidney transplantation , microbiology and biotechnology , immunology , biology , gene expression , peptidylprolyl isomerase , genetics , isomerase
Background: The cyclophilin A (CypA) ‐ cyclosporine (CsA) complex promotes immune response. The variation at the CypA gene could explain CsA‐pharmacokinetics and clinical outcomes among CsA‐treated patients. Methods: The study included 290 kidney transplanted patients (65% male; mean age 51 ± 15 yr), treated with CsA. The five CypA‐ exons and the promoter region were analysed through single‐strand conformation analysis, denaturing high performance liquid chromatography, and direct sequencing. The effect of a promoter polymorphism (−11 G/C) on gene expression was analysed in cell‐cultures. Results: We found two polymorphisms in the promoter (−11 G/C) and exon 1 (+36 G/A). Genotype frequencies did not differ between patients according to their pharmacokinetics status. In vitro studies showed that −11 G/C affected gene expression. The −11 G allele was significantly associated with clinical nephrotoxicity (p = 0.006). The strongest predictors for nephrotoxicity were a donor age ≥55 yr, and the promoter GG + GC genotypes. Conclusions: Our work suggests that a CypA‐promoter polymorphism (−11 G/C) could be associated with clinical nephrotoxicity. Replication of this study in other populations is necessary to define the role of CypA‐variants in the main clinical outcomes among CsA‐treated kidney‐transplanted patients.