Genetic predisposition and renal allograft failure: implication of non-HLA genetic variants

Renal allograft rejection or dysfunction often results in graft failure, and remains the major obstacle in the success of renal transplantation. Various immunological and nonimmunological factors are involved in allograft rejection. In addition to human leukocyte antigen loci, several genetically controlled molecules have been identified in recent years as playing important roles in the process of rejection. Genetic variants in genes encoding different T-helper (Th) type 1 and Th2 cytokines, chemokines and their receptors, growth factors, molecules of the renin-angiotensin system, enzymes of the homocysteine pathway, and proteins acting as substrates of immunosuppressive drugs impact on the success of engraftment and highlight the concept of genetic predisposition to allograft rejection. This review evaluates specific genetic variants and their functional roles in graft failure, with an emphasis on the latest methodologies available for genotyping, and appropriate strategies to enable them to become a tool of predictive and individualized medicine to ensure better transplant outcome.