Cytokine Gene Polymorphism in Heart Transplantation: A Review

F.   J.   Bijlsma; A.   H.   Bruggink; F.   H.J.   Gmelig-Meyling; R.A.   de   Weger

doi:10.2174/1389202033490411

Abstract

Cardiovascular disease is the most common cause of death in todays society. Heart transplantation is the only available treatment for patients suffering from end-stage congestive heart failure (CHF). Causes underlying the development of CHF are still unknown, but it has been suggested that proinflammatory cytokines play an important role. In the context of transplantation, proinflammatory T-helper 1 cytokines like TNF-α and IL-2 that mediate the cellular immune response are believed to be involved in acute graft rejection. On the other hand, Th2 cytokines, like IL-4, IL-6 and IL-10, induce tolerance, by down-regulating the Th1 response and cytokine production. Cytokine release by macrophages, lymphocytes and other cell types in the microenvironment of the graft, especially the balance between Th1 and Th2, is thought to be critical for the development of acute rejection. Production of cytokines has been shown to be under genetic control of single nucleotide polymorphisms (SNP) in mainly the promoter regions of cytokine genes. Genotypes of these SNP were shown to control the differential production of these cytokines, leading to a wide variety of cytokine patterns among individuals. Since levels of these cytokines affect the Th1 / Th2 balance, genotypes may be related to acute allograft rejection. Many studies have shown an association between cytokine gene polymorphisms and the development of several infections, allergies and autoimmune diseases. Also, associations between SNP in different cytokine genes and transplant rejection have been extensively studied. In our lab, SNP in the genes of TNF-α, TGF-β, IL- 4 and IL-10 were studied in a panel of 70 cardiac transplant patients and 61 of their donors. These data are discussed in the context of literature data.

Keywords: cytokine gene, gene polymorphism, heart transplantation, single nucleotide polymorphism, snp