Human Leukocyte Antigen-G (HLA-G) is a non-classical class 1b protein, whose gene is located on chromosome 6 (6p21.31). HLA-G inhibits the immune cells' cytotoxic activity by interacting with specific receptors on their membranes. Since it is a naturally occurring immune modulator, HLA-G has been investigated in transplantation. Indeed, a number of investigations reveal that HLA-G expression is influenced by genetic polymorphisms and in turn, those polymorphisms are associated with detrimental or beneficial outcomes in various pathological situations. The present review introduces the HLA-G molecule, the gene and its polymorphisms. It focuses on the expression of HLA-G and the role of polymorphisms primarily in heart transplant outcomes, secondarily in other transplant organs, as well as the role of the allograft and effect of medical therapy. We discuss the limitations in HLA-G transplant investigations and future directions. The immune inhibiting activity of HLA-G has a great deal of potential for its utilization in enhancing diagnostic, preventive and therapeutic strategies against rejection in the setting of transplantation.
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