NFKB1 promoter polymorphism: A new predictive marker of cytomegalovirus infection after kidney transplantation

Transpl Infect Dis. 2019 Feb;21(1):e13027. doi: 10.1111/tid.13027. Epub 2018 Dec 6.

Abstract

Introduction: Cytomegalovirus (CMV) infection represents a common cause of morbidity and mortality in kidney transplant recipients (KTR). The NF-kB signaling pathway is highly involved in the pathogenesis of CMV infection. The -94ins/delATTG functional polymorphism in the promoter of NFKB1 has been associated with low intracellular levels of the protein and high incidence of inflammatory and autoimmune disease. In this study, we evaluated the association of this NFKB1 polymorphism with the risk of CMV infection.

Methods: CMV infection was defined as virus isolation or detection of viral antigens or nucleic acid in any body fluid or tissue specimen. Using Cox regression and survival analysis, we analyzed the association between the polymorphism and CMV infection as well as recurrence in the first 12 months after transplantation.

Results: We analyzed the -94ins/delATTG NFKB1 polymorphism of 189 KTRs. The 65% of CMV infections occurred in ins/ins group. Survival free from CMV infection was 54.7% for ins/ins group and 79.4% for deletion carriers one year after transplantation (P < 0.0001). At multivariate regression, deletion carriers showed a lower risk of CMV infection and recurrence with respect to ins/ins KTRs (HR = 0.224 P = 0.0002; HR = 0.307, P = 0.012, respectively).

Conclusions: In conclusion, pretransplantation screening for NFKB1 -94ins/delATTG polymorphism may predict CMV infection and improve the management of patients at higher risk of infection in the post-transplant period.

Keywords: NFKB1 polymorphism; cytomegalovirus infection; preemptive therapy; renal transplantation.

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / genetics
  • Cytomegalovirus Infections / virology
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Humans
  • INDEL Mutation
  • Incidence
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • NF-kappa B p50 Subunit / genetics*
  • Polymorphism, Genetic
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / epidemiology
  • Postoperative Complications / genetics
  • Postoperative Complications / virology
  • Predictive Value of Tests
  • Preoperative Care / methods
  • Prognosis
  • Promoter Regions, Genetic / genetics*

Substances

  • Biomarkers
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human