Transforming Growth Factor-beta Polymorphisms and Cardiac Allograft Rejection

• Published in: The Journal of heart and lung transplantation Vol. 28; no. 10; pp. 1057 - 1062
• Main Authors: Benza, Raymond L., MD, Coffey, Christopher S., PhD, Pekarek, Dawn M., MD, Barchue, Joseph P., PA, Tallaj, Jose A., MD, Passineau, Michael J., PhD, Grenett, Hernan E., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2009; Elsevier
• Subjects: Adult; Biological and medical sciences; Cardiology. Vascular system; Female; Follow-Up Studies; Genetic Predisposition to Disease - genetics; Genotype; Graft Rejection - genetics; Heart Transplantation - adverse effects; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Multivariate Analysis; Polymorphism, Genetic - genetics; Retrospective Studies; Risk Factors; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Transforming Growth Factor beta - genetics; Transplantation, Homologous; Heart; Graft(material); Transforming growth factor β; Transplantation; Homotransplantation; Phlebology; Rejection; Treatment; Surgery; Graft; Circulatory system; Cardiology; Polymorphism
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2009.06.001

Background Cytokine gene polymorphisms regulate cytokine expression. We analyzed transforming growth factor-beta (TGF-β) allelic variation in codon 25 in susceptibility to acute rejection episodes in cardiac transplant recipients. Methods Between June 1997 and December 2001, 123 de novo heart transplants were performed at UAB with analysis based on 109 patients. Clinical and laboratory data were recorded at intervals up to 1 year post-transplant. Recipient genotypes for TGF-β (codon 25) were determined using polymerase chain reaction (PCR) sequence-specific primers. Correlations between TGF-β genotypes and acute rejection were made using Kaplan–Meier plots and parametric hazard models. Results Of the patients enrolled, 72% had at least one rejection and 46% had multiple rejections in the first year post-transplant. Among those ≥55 years of age at transplant, patients with the GG genotype had significantly fewer rejections as compared to those with the CC or GC genotype (1.25 vs 2.5, p < 0.01). There was no difference in risk of rejection between the genotype groups among patients <50 years of age at transplant ( p = 0.43). Similar results were observed when we used time to cumulative Grade 2R or greater rejection as the outcome. Conclusion The GG TGF-β genotype may protect against acute rejection in older recipients during the first year after transplant.