A comprehensive systematic review published in Cardiogenetics has highlighted the growing importance of pharmacogenetics in optimizing immunosuppressive therapy for heart transplant recipients. The review examined 64 clinical studies, revealing how genetic variations significantly influence the effectiveness, dosing, and safety of standard immunosuppressant drugs.

Current post-transplant immunosuppressive regimens typically include calcineurin inhibitors (like tacrolimus), corticosteroids, and antimetabolite agents or mTOR inhibitors. However, patient response varies widely; a difference now increasingly attributed to genetic factors.

The review found that variants in genes such as CYP3A4/5 and POR*28 affect tacrolimus metabolism, with CYP3A4/5 variants linked to higher required doses and POR*28 variants to lower doses. Polymorphisms in transporter genes like ABCB1, ABCC2, SLCO1B1, and SLC13A1 also influence drug absorption, distribution, and toxicity. Notably, ABCC2 rs717620 was associated with an increased risk of graft rejection in pediatric patients.

Beyond drug metabolism, polymorphisms in immune-regulating genes such as HLA-G, TNF-α, and TGF-β were linked to heightened rejection risks and altered immune responses.