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Background  To explore associations between  PON1  rs854560, rs662, 705,379, HCV clearance, and interactions between tested  PON1  single nucleotide variants (SNVs) and interferon-λ4 gene ( IFNL4 ) rs368234815 variant in hemodialyzed individuals.    Methods  The study included 83 HD individuals who spontaneously resolved HCV infection (all had known  IFNL4  rs368234815 variant) and 104 individuals with persistently positive blood tests for HCV RNA (102 were  IFNL4  rs368234815 variant successfully genotyped). We genotyped  PON1  by high-resolution melt analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). We used a logistic regression model to assess the association between genetic data and HCV outcome while adjusting for clinical confounding variables. Epistatic interactions between tested  PON1  SNVs and  IFNL4  rs368234815 were analyzed by the multifactor dimensionality reduction method.    Results  In the recessive inheritance model,  PON1  rs662 GG (OR 9.94, 95% CI 1.20–82.7,  P  = 0.022) and rs854560 TT (OR 4.31, 95% CI 1.62–11.5,  P  = 0.003) genotypes were associated with a higher probability for HCV clearance. The haplotype composed of rs662A_rs854560A_rs705379 was not associated with spontaneous HCV clearance. The  IFNL4  rs368234815 TT/TT variant was equally distributed among individuals bearing different  PON1  SNVs. The epistatic gene–gene analysis did not reveal the interaction between tested  PON1  SNVs and  IFNL4  rs368234815 ( P  = 0.094). Regression model, including the  PON1  rs662 GG genotype, the  PON1  rs854560 genotype, the  IFNL4  rs368234815 TT/TT genotype, age at RRT onset, RRT duration, and chronic glomerulonephritis as possible explanatory variables for spontaneous HCV clearance, showed that significant predictors of spontaneous HCV clearance were the  IFNL4  rs368234815 TT/TT genotype (OR 2.607, 95% CI 1.298—5.235,  P  = 0.007),  PON1  rs854560 TT (OR 6.208, 1.962–19.644,  P  = 0.002),  PON1  rs662 GG (OR 10.762, 1.222–94.796,  P  = 0.032), and RRT duration (OR 0.930, 95% CI 0.879–0.984,  P  = 0.011).    Conclusion  In HD individuals,  PON1  rs662 GG and rs854560 TT are associated with a higher frequency of spontaneous HCV clearance.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12879-021-06597-4.

Paraoxonase 1 gene (PON1) variants concerning hepatitis C virus (HCV) spontaneous clearance in hemodialysis individuals: a case–control study