Interferon-λ3 Gene Polymorphic Variants, rs4803217 and rs12980275, Responsiveness to HBV Vaccine and Outcome of HBV and HCV Exposure in Hemodialyzed Patients

Abstract

Background: In non-uremic populations, rs4803217 in the IFNL3 messenger RNA 3’ untranslated region or rs12980275 downstream of IFNL3 is connected with the spontaneous or therapeutic clearance of HCV and HBV, and rs12980275 is correlated with plasma IFN-λ3 levels. Moreover, rs12980275 is associated with the sustained virological response following antiviral therapy of chronic hepatitis C in hemodialysis patients. Objectives: We investigated IFNL3 polymorphisms, rs4803217 and rs12980275, for association with responsiveness to HBV vaccine and natural consequences of HBV and HCV exposure among hemodialyzed individuals. Methods: The capacity to produce protective anti-HBs titers was recognized if they were ≥ 10 IU/L after vaccination or natural exposure. The IFNL3 rs4803217 (G>T) and rs12980275 (A>G) genetic variants were analyzed using a high-resolution melting curve method in 1,337 hemodialysis subjects. Plasma IFN-λ3 was determined in 188 individuals using ELISA. The Kaplan-Meier method was applied for the analysis of survival probability. Results: The tested polymorphisms did not show associations with the capacity to generate protective anti-HBs titers after HBV vaccination or exposition and self-limitation of HBV exposure. Natural HCV clearance was connected with the IFNL3 rs4803217 GG genotype (OR: 3.036, 95% CI: 1.544 - 5.969, P = 0.001) and haplotypes comprising at least two more frequent alleles but without any variant allele of IFNL3/IFNL4 genetic variants (P < 0.05). Plasma IFN-λ3 levels were not directly influenced by IFNL3 rs4803217 and rs12980275, but differed concerning HBV/HCV serum markers (P = 0.00005) and firmly correlated with anti-HBs titers (r = 0.537, P = 4.15E-16). Both tested polymorphisms were not significantly associated with the survival of hemodialysis patients. Conclusions: Genotyping IFNL3 rs4803217 may be advantageous in the prognosis of natural HCV clearance but does not predict the self-limitation of HBV exposure, responsiveness to HBV vaccine, or hemodialysis patients’ mortality.