Related Experiment Video
Updated: Jun 20, 2026
09:25
An Immunological Model for Heterotopic Heart and Cardiac Muscle Cell Transplantation in Rats
Published on: May 8, 2020
Transforming growth factor-beta polymorphisms and cardiac allograft rejection
Raymond L Benza1, Christopher S Coffey, Dawn M Pekarek
1Division of Cardiovascular Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. rbenza@wpahs.org
Summary
The GG genotype of transforming growth factor-beta (TGF-beta) may protect older heart transplant recipients from acute rejection in the first year post-transplant. This finding highlights genetic influences on transplant outcomes.
Area of Science:
- Immunogenetics
- Transplant Medicine
- Cardiology
Background:
- Cytokine gene polymorphisms influence gene expression.
- Transforming growth factor-beta (TGF-beta) plays a role in immune regulation.
- Acute rejection is a significant complication in cardiac transplantation.
Purpose of the Study:
- To investigate the association between transforming growth factor-beta (TGF-beta) gene polymorphisms at codon 25 and acute rejection episodes in heart transplant recipients.
- To determine if specific TGF-beta genotypes impact the risk of acute rejection.
- To explore age-related differences in the effect of TGF-beta genotypes on transplant outcomes.
Main Methods:
- Analysis of 109 de novo heart transplant recipients between June 1997 and December 2001.
- Determination of recipient TGF-beta (codon 25) genotypes using polymerase chain reaction (PCR) sequence-specific primers.
- Correlation of TGF-beta genotypes with acute rejection using Kaplan-Meier plots and parametric hazard models.
Main Results:
- 72% of patients experienced at least one rejection episode within the first year post-transplant.
- Older recipients (≥55 years) with the GG genotype had significantly fewer rejections compared to CC or GC genotypes (1.25 vs 2.5, p < 0.01).
- No significant difference in rejection risk was observed between genotype groups in younger recipients (<50 years, p = 0.43).
Conclusions:
- The GG TGF-beta genotype may confer a protective effect against acute rejection in older cardiac transplant recipients.
- Age appears to be a modifying factor in the relationship between TGF-beta genotype and transplant rejection.
- These findings suggest a potential role for immunogenetic profiling in personalized transplant management.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
01:24Tissue Transplantation
Tissue transplantation is a significant medical procedure involving the transfer of cells, tissues, or organs from a donor to a recipient, with the primary aim of restoring lost functions. This procedure is crucial in treating a broad spectrum of diseases, including kidney diseases, liver failure, heart disease, and certain types of cancers.
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...
The Biology of Tissue Transplantation
The biology of tissue transplantation hinges on the Major Histocompatibility Complex (MHC) molecules. These molecules...
01:40Cell-mediated Immune Responses
Overview
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:22Bone Marrow Sampling and Transplants
Bone marrow transplant is a potential cure for several diseases, including cancer and specific genetic disorders. Notably, this procedure is applicable for patients suffering from aplastic anemia, certain types of leukemia, severe combined immunodeficiency disease (SCID), Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, thalassemia, sickle-cell disease, and certain cancers.
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy the...
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy the...