Investigation of the Association Between Paraoxonase-1 Gene Polymorphisms and Response to Therapy in Chronic Hepatitis C Patients

Kıratlı, Kazım; Gül, Hanefi Cem; Artuk, Cumhur; Kozan, Salih; Öztuna, Ali; Tunca, Yusuf; Eyigün, Can Polat

doi:10.5578/mb.8202

Cited by 1 publication

(2 citation statements)

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“…On the other hand, downregulation of PON-1 was suggested as an indicator for predicting the poor survival of individuals with hepatocellular carcinoma [ 32 ]. Pegylated interferon and ribavirin treatment efficacy were not demonstrated as dependent on PON1 SNVs [ 10 ]. Taking into account PON1 SNVs functionality, they could be relevant as candidates for investigation of HCV infection outcome.…”

Section: Introductionmentioning

confidence: 99%

“…These PON1 SNVs were the most frequently analyzed in the general population, and also in HD individuals, concerning mainly atherosclerosis-related complications [ 23 ], antioxidant activity [ 24 ], diabetes mellitus [ 35 ], and dyslipidemia [ 36 ]. Data related to HCV infection concerning PON1 SNVs are very rare in non-uremic individuals [ 9 , 10 ]. The uremic milieu of dialyzed individuals might influence the transcription and translation of PON1 SNVs, probably downregulate, as serum PON-1 activity and concentration are usually decreased in uremia.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%