Non-HLA Genetic Factors and Their Influence on Heart Transplant Outcomes: A Systematic Review

BACKGROUND: Improvement of immunosuppressive therapies and surgical techniques has increased the survival rate after heart transplantation. Nevertheless, a large number of patients still experience complications, such as allograft rejection, vasculopathy, kidney dysfunction, and diabetes in response to immunosuppressive therapy. Variants in HLA genes have been extensively studied for their role in clinical outcomes after transplantation, whereas the knowledge about non-HLA genetic variants in this setting is still limited. Non-HLA polymorphisms are involved in the metabolism of major immunosuppressive therapeutics and may play a role in clinical outcomes after cardiac transplantation. This systematic review summarizes the existing knowledge of associations between non-HLA genetic variation and heart transplant outcomes. METHODS: The current evidence available on genetic polymorphisms associated with outcomes after heart transplantation was identified by a systematic search in PubMed and Embase. Studies reporting on polymorphisms significantly associated with clinical outcomes after cardiac transplantation were included. RESULTS: A total of 56 studies were included, all were candidate gene studies. These studies identified 58 polymorphisms in 36 genes that were associated with outcomes after cardiac transplantation. Variants in TGFB1, CYP3A5, and ABCB1 are consistently replicated across multiple studies for various transplant outcomes. CONCLUSIONS: The research currently available supports the hypothesis that non-HLA polymorphisms are associated with clinical outcomes after heart transplantation. However, many genetic variants were only identified in a single study, questioning their true effect on the clinical outcomes tested. Further research in larger cohorts with well-defined phenotypes is warranted.