Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants

While the influence of cytokine gene polymorphisms on immunologic complications after organ transplantation is widely evaluated, little is known about predictive value of cytokine genotype for the development of nonimmunologic post-transplant complications: hypertension, dyslipoproteinemia, diabetes mellitus, hyperuricemia.

The -1082IL-10, -308TNF-alpha, transforming growth factor-beta1 (TGF-beta1) (codon 10, 25), -174IL-6, +874IFN-gamma gene single nucleotide polymorphisms (SNP) were studied in 278 long-term renal transplants by polymerase chain reaction-sequence specific primer (PCR-SSP) with respect to nonimmunologic post-transplant complications.

Significant association of the TGF-beta (codon 25) GG genotype with hyperuricemia (P= 0.0013) and dyslipoproteinemia (P= 0.0171) was found. The TGF-beta1 (codon 25) CG genotype was detected more frequently in patients with normal uric acid levels. The +874IFN-gamma AA genotype was associated with type 2/steroid-induced diabetes (P= 0.0127). Frequency of the -1082IL-10 AG genotype was significantly higher in hyperuricemic patients versus controls (P= 0.0022). No associations of polymorphisms in the tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), TGF-beta codon 10 genes with hyperuricemia, dyslipoproteinemia, or diabetes were detected. We failed to observe significant differences in cytokine genotype distribution between hypertensive and normotensive patients.

We established an association of particular cytokine genotypes with nonimmunologic post-transplant complications. This supports an idea that assessment of cytokine SNPs may allow more accurate prediction of nonimmunologic complications and appropriate adjustment of pre-emptive treatments in long-term transplant patients.