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Tumor necrosis factor gene polymorphism and cardiac allograft vasculopathy

Journal article
Authors Lisa Ternström
Anders Jeppsson
Anne Ricksten
Folke Nilsson
Published in J Heart Lung Transplant
Volume 24
Issue 4
Pages 433-8
ISSN 1053-2498 (Print)
Publication year 2005
Published at Cardiovascular Institute
Institute of Laboratory Medicine, Dept of Clinical Chemistry/Transfusion Medicine
Pages 433-8
Language en
Keywords Adult, Coronary Angiography, Coronary Arteriosclerosis/*blood/etiology/radiography, Coronary Vessels/*pathology, Female, Follow-Up Studies, Gene Frequency, Genetic Markers, Graft Rejection/blood/prevention & control, Graft Survival/genetics, Heart Transplantation/*adverse effects/mortality, Humans, Immunosuppressive Agents/therapeutic use, Male, Middle Aged, Polymerase Chain Reaction, *Polymorphism, Genetic, Prospective Studies, Survival Rate, Transplantation, Homologous, Tumor Necrosis Factor-alpha/biosynthesis/*genetics
Subject categories Surgery


BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after cardiac transplantation. Tumor necrosis factor-alpha (TNF-alpha) may be a key factor in the development of CAV. Two bi-allelic polymorphisms associated with high TNF-alpha production have been identified in the TNF gene locus, TNFA1/2, at position -308 and TNFB1/2 at +252. We hypothesized that recipient TNFA2 and TNFB2 homozygosity is associated with the development of CAV after heart transplantation. METHODS: TNF gene polymorphisms were analyzed by multiplex fluorescent solid-phase mini-sequencing in 70 cardiac transplant recipients. Recipients homozygous for TNFA2 or TNFB2 (Group A, n = 29) were compared with recipients heterozygous or homozygous for TNFA1 and TNFB1 (Group B, n = 41). Coronary arteriography was performed annually or when indicated. Cumulative freedom from CAV and survival was calculated according to the Kaplan-Meier test. RESULTS: Mean follow-up was 3.8 +/- 0.3 years. In Group A, 11 of 29 recipients (38%) developed CAV compared with 9 of 41 (22%) in Group B (p = 0.12). Cumulative freedom from CAV at 3 years was 42% in Group A and 80% in Group B (p = 0.043). In Group A, 11 of 29 recipients (38%) died during follow-up compared with 4 of 41 (10%) in Group B (p = 0.006). Cumulative survival at 3 years was 72% in Group A and 93% in Group B (p = 0.003). CONCLUSIONS: The results suggest that TNFA2 and TNFB2 allele homozygosity is associated with cardiac allograft vasculopathy and mortality in heart transplant recipients.

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