BACKGROUND: Epstein-Barr virus (EBV) is associated with most cases of the post-transplant lymphoproliferative disorders developed during the first year after transplantation. The high EBV DNA load constitutes a major risk for the development of EBV-related lymphoproliferations. However, among transplant recipients there are patients with a chronically high viral load (CHVL) who do not develop lymphoproliferations. The polymorphism within cytokine genes might influence the susceptibility to, and contribute to the pathogenesis of the disease. OBJECTIVES: The aim of this study was to analyze the genetic polymorphism in the selected cytokines with regard to EBV infection outcome in children after liver transplantation (LTx). STUDY DESIGN: Thirteen cytokine/cytokine receptor polymorphisms were genotyped in 170 children after LTx, and related to: EBV DNAemia, CHVL onset and the length of CHVL carriage. RESULTS: The study revealed: the protective effect of rare homozygous and heterozygous IL-1β-511 and IL-1 receptor antagonist (IL-1RN VNTR) genotypes against viremia within the first year after LTx (OR=0.28, p=0.0007 and OR=0.35, p=0.009, respectively); the protective effect of CC chemokine ligand 2 (CCL2)+1543CT and TT genotypes against CHVL onset (OR=0.38, p=0.042); and the prolonged CHVL-resolution in IL12B 3'untranslated region (3'UTR) AC individuals (p=0.034). CONCLUSIONS: This data suggests that carriage of IL-1β-511CT/TT and/or IL-1RN VNTR 1.2/2.2 genotype may be beneficial for combating EBV infection. This is the first study reporting the association of CCL2 and IL12B gene polymorphisms with the CHVL carriage in pediatric LTx recipients.
BACKGROUND: Epstein-Barr virus (EBV) is associated with most cases of the post-transplant lymphoproliferative disorders developed during the first year after transplantation. The high EBV DNA load constitutes a major risk for the development of EBV-related lymphoproliferations. However, among transplant recipients there are patients with a chronically high viral load (CHVL) who do not develop lymphoproliferations. The polymorphism within cytokine genes might influence the susceptibility to, and contribute to the pathogenesis of the disease. OBJECTIVES: The aim of this study was to analyze the genetic polymorphism in the selected cytokines with regard to EBV infection outcome in children after liver transplantation (LTx). STUDY DESIGN: Thirteen cytokine/cytokine receptor polymorphisms were genotyped in 170 children after LTx, and related to: EBV DNAemia, CHVL onset and the length of CHVL carriage. RESULTS: The study revealed: the protective effect of rare homozygous and heterozygous IL-1β-511 and IL-1 receptor antagonist (IL-1RN VNTR) genotypes against viremia within the first year after LTx (OR=0.28, p=0.0007 and OR=0.35, p=0.009, respectively); the protective effect of CC chemokine ligand 2 (CCL2)+1543CT and TT genotypes against CHVL onset (OR=0.38, p=0.042); and the prolonged CHVL-resolution in IL12B 3'untranslated region (3'UTR) AC individuals (p=0.034). CONCLUSIONS: This data suggests that carriage of IL-1β-511CT/TT and/or IL-1RN VNTR 1.2/2.2 genotype may be beneficial for combating EBV infection. This is the first study reporting the association of CCL2 and IL12B gene polymorphisms with the CHVL carriage in pediatric LTx recipients.
Authors: Niquelle Brown Wadé; Cindy M Chang; David Conti; Joshua Millstein; Christine Skibola; Alexandra Nieters; Sophia S Wang; Silvia De Sanjose; Eleanor Kane; John J Spinelli; Paige Bracci; Yawei Zhang; Susan Slager; Jun Wang; Henrik Hjalgrim; Karin Ekstrom Smedby; Elizabeth E Brown; Ruth F Jarrett; Wendy Cozen Journal: Cancer Causes Control Date: 2020-03-02 Impact factor: 2.532