The Interferon-Gamma +874 A/T Polymorphism Is Not Associated With CMV Infection After Kidney Transplantation

Front Immunol. 2020 Jan 8:10:2994. doi: 10.3389/fimmu.2019.02994. eCollection 2019.

Abstract

The +874 A/T polymorphism in the interferon gamma (IFNG) gene has been associated with Cytomegalovirus (CMV) infection risk in lung and kidney transplant recipients. To replicate this association, we performed a retrospective observational study of this polymorphism and immunosuppressive therapies considering the prophylactic treatment in 600 consecutive kidney transplanted recipients. We found no association of the aforementioned polymorphism with CMV infection in univariate and multivariate analyses regardless of the prophylactic treatment. In addition, the immunosuppressive treatment with mammalian target of rapamycin inhibitors (imTOR) showed a protective effect in all patients independently of prophylaxis. Moreover, in the adjusted model, we found interactions between prophylaxis with high-risk (Donor+/Recipient-, D+/R-) status (p-interaction = 0.01), with thymoglobulin induction therapy (p-interaction = 0.03) and with thymoglobulin anti-rejection therapy (p-interaction = 0.002). Data also revealed that prophylaxis was not an advantage in the not D+/R- and without thymoglobulin therapy group (HR = 0.98, p = 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV infection group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, p < 0.001). In conclusion, the IFNG +874 polymorphism is not a predictive marker of CMV infection. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV infection, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy.

Keywords: IFNG polymorphism; cytomegalovirus; immunosuppression; kidney transplantation; prophylaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / etiology*
  • Cytomegalovirus Infections / prevention & control
  • Disease Susceptibility*
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Interferon-gamma / genetics*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / methods
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Retrospective Studies

Substances

  • Cytokines
  • Interferon-gamma