Polymorphism of the transforming growth factor–beta 1 gene correlates with the development of coronary vasculopathy following cardiac transplantation
Background: Expression of transforming growth factor–β1 (TGF-β1) is central to vascular repair due to its effects on smooth muscle cell, monocyte/macrophage, leucocyte, and extracellular matrix accumulation and proliferation. Genetic polymorphism at position +915 of the TGF-β1 gene determines the de...
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Published in | The Journal of heart and lung transplantation Vol. 19; no. 6; pp. 551 - 556 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Elsevier Inc
01.06.2000
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | Background: Expression of transforming growth factor–β1 (TGF-β1) is central to vascular repair due to its effects on smooth muscle cell, monocyte/macrophage, leucocyte, and extracellular matrix accumulation and proliferation. Genetic polymorphism at position +915 of the TGF-β1 gene determines the degree of cytokine production in response to injury. We investigated this allelic variation on the development of cardiac transplant–related coronary vasculopathy (CV).
Using sequence-specific primers to the TGF-β1 gene region of interest, a polymerase chain reaction (PCR) and gel electrophoresis identified the genotype in 129 cardiac transplant recipients. An association was sought between the presence of a high- (GG) or low/intermediate-producing (CC/GC) genotype and the development of coronary vasculopathy diagnosed by coronary angiography.
C allele carriers made up 10.9% of the recipient population but were significantly less likely to develop coronary vasculopathy (p = 0.0361). Mean time to diagnosis was 1240.5 days in G homozygotes relative to 2266.5 days in C allele carriers (p = 0.002). Pre- and 1-year posttransplant clinical variables were equivalent between the 2 groups. Multivariate analysis identified the GG genotype (p = 0.042, hazard ratio 3.01, [95% CI, 1.056–10.99]), donor age (p = 0.002, hazard ratio 1.063, [95% CI, 1.029–1.097]), and number of acute-rejection episodes of grade 3 or greater in the first year (p = 0.029, hazard ratio 1.11, [95% CI, 1.05–1.26]) as significant predictors of vasculopathy.
This study demonstrates a correlation between a high-producing TGF-β1 genotype and an earlier onset of cardiac-transplant coronary vasculopathy. This gives an important insight into the pathophysiology of cardiac transplant vasculopathy and suggests new treatment options. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1053-2498 1557-3117 |
DOI: | 10.1016/S1053-2498(00)00114-5 |