Kidney Transplantation, Polymorphisms of IL-18, and Other Pro-Inflammatory Genes and Late Post-Transplant Outcome.
BACKGROUND
Functional polymorphisms of molecules involved in immune-mediated mechanisms of allograft rejection could be predictive of increased risk for early and late post-transplant complications. In the past years, the challenge for long-term graft survival in kidney recipients is the implementation of personalized approaches. In this study, effects of interleukin (IL)-18-137G/C (rs187238), -607C/A (rs1946518), and other pro-inflammatory cytokine gene polymorphisms (tumor necrosis factor [TNF]-α-308G/A, rs1800629, IL-6-174G/C, rs1800795, and interferon [IFN]-γ+874A/T, rs2430561) on the main post-transplant risk parameters and diseases (metabolic, cardiovascular, infective, and chronic allograft rejection) were assessed in kidney-transplanted patients.


METHODS
One hundred seventy-nine transplanted patients were retrospectively analyzed for clinical and biochemical parameters and onset of post-transplant complications. Taqman allelic discrimination and PCR-SSP (polymerase chain reaction-sequence specific primers) techniques were used for genotyping.


RESULTS
No predictive effects of allele and genotypes of IL-18-607C/A, TNF-α-308G/A, IL-6-174G/C, and IFN-γ+874A/T gene polymorphisms and onset of risk factors and late complications were evidenced. However, Kaplan-Meier analysis evidenced a weak effect of IL-18-137G/C genotypes on graft survival.


CONCLUSIONS
Analyzing associations between some pro-inflammatory cytokine gene polymorphisms and onset of the most relevant risk factors and late complications of kidney transplant, results suggested a possible impact of IL-18-137G/C genotypes on graft survival, which deserves further studies.
CNR-Institute of Translational Pharmacology, UOS L'Aquila, Italy. Electronic address: daniela.piancatelli@cnr.it.
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Piancatelli
CRT-Regional Center for Organ Transplantation, S. Salvatore Hospital, L'Aquila, Italy.
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Maccarone
CNR-Institute of Translational Pharmacology, UOS L'Aquila, Italy.
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Colanardi
CNR-Institute of Translational Pharmacology, UOS L'Aquila, Italy.
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Sebastiani
Transplant Unit, "S. Salvatore" Hospital, L'Aquila, Italy.
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Clemente
Transplant Unit, "S. Salvatore" Hospital, L'Aquila, Italy.
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Iesari
Transplant Unit, "S. Salvatore" Hospital, L'Aquila, Italy.
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Di Pietro
Transplant Unit, "S. Salvatore" Hospital, L'Aquila, Italy.
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Lai
Transplant Unit, "S. Salvatore" Hospital, L'Aquila, Italy; Department of Clinical Sciences and Biotechnology, University of L'Aquila, Italy.
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Famulari
Transplant Unit, "S. Salvatore" Hospital, L'Aquila, Italy; Department of Clinical Sciences and Biotechnology, University of L'Aquila, Italy.
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Pisani
D000328:Adult; D000483:Alleles; D016207:Cytokines / Q000235:genetics; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; C000589760:IL18 protein, human; C508600:IL6 protein, human; D020382:Interleukin-18; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha