The effect of cytokine gene polymorphisms on pediatric heart allograft outcome
| Autor: | Frank A. Pigula, Cindy Sturchioĉ, Gerald Boyle, George V. Mazariegos, Pamela Bowman, Adriana Zeevi, Susan A. Miller, Mohammed R. Awad, Steven C. Gribar, Bartley P. Griffith, Yuk M. Law, Mamun Ahmed, Steven A. Webber, Joan Martell |
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| Rok vydání: | 2001 |
| Předmět: |
Pulmonary and Respiratory Medicine
Graft Rejection Adolescent medicine.medical_treatment Population Polymorphism (computer science) Genotype Biopsy medicine Humans education Child Transplantation education.field_of_study Polymorphism Genetic medicine.diagnostic_test business.industry Graft Survival Interleukin Prognosis Cytokine Immunology Cytokines Heart Transplantation Surgery Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine business |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 20(6) |
| ISSN: | 1053-2498 |
| Popis: | Background Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcome. Several studies have shown that the production of cytokines varies among individuals and these variations are determined by genetic polymorphisms, most commonly within the regulatory region of the cytokine gene. The aim of this study was to assess the effect of these allelic variations on acute rejection after pediatric heart transplantation. Method We performed cytokine genotyping using polymerase chain reaction-sequence specific primers in 93 pediatric heart transplant recipients and 29 heart donors for the following functional polymorphisms: tumor necrosis factor-α (TNF-α) (-308), interleukin (IL)-10 (-1082, -819, and -592), TGF-β1 (codon 10 and 25), IL-6 (-174), and interferon-γ (INF-γ) (+874). The distribution of polymorphisms in this population did not differ from published controls. The patients were classified as either non-rejecters (0 or 1 episode) or rejecters (> 1 episode) based on the number of biopsy proven rejection episodes in the first year after transplantation. Results Forty-two of the 69 TNF-α patients (61%) in the low producer group were non-rejecters, while 9 of the 24 (37.5%) with high TNF-α were non-rejecters ( p = 0.047). In contrast, IL-10 genotype showed the opposite finding. Forty-two of the 66 patients (64%) in the high and intermediate IL-10 group were non-rejecters, while 9 of the 26 (35%) in the low IL-10 group were non-rejecters ( p = 0.011). The combination of low TNF-α with a high or intermediate IL-10 genotype was associated with the lowest risk of rejection (34/49 or 69% non-rejecters). Neither the distribution of the IL-6, INF-γ, and TGF-β1 genotype in recipients nor the donor genotype showed any association with acute rejection. Conclusion Genetic polymorphisms that have been associated with low TNF-α and high IL-10 production are associated with a lower number of acute rejection episodes after pediatric heart transplantation. |
| Databáze: | OpenAIRE |
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