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Updated: Jul 3, 2026

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
A search for cyclophilin-A gene variants in cyclosporine A-treated renal transplanted patients
Grace Tamara Moscoso-Solorzano1, Francisco Ortega, Isabel Rodríguez
1Servicio de Nefrología-Hospital Central de Asturias, Oviedo, Spain.
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 > or =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.
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