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Abstract: PO0810

Paraoxonase 1 Gene Variants Concerning Spontaneous HCV Clearance in Hemodialysis Patients

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Grzegorzewska, Alicja E., Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
  • Mostowska, Adrianna, Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
  • Warchol, Wojciech J., Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
  • Jagodzinski, Pawel P., Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
Background

We aim to explore associations between three PON1 SNVs (rs705379, rs854560, and rs662) and spontaneous clearance of HCV infection in uremic patients treated with maintenance HD. Epistatic interactions between tested PON1 SNVs and the IFNL4 variant rs368234815 were also investigated.

Methods

The study included 83 HD patients who spontaneously resolved HCV infection (all had known IFNL4 rs368234815 variant) and 104 subjects with persistently positive blood tests for HCV RNA (102 were successfully genotyped for IFNL4 rs368234815 variant). We genotyped PON1 by HRM method (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). We used a regression model including genetic and clinical data, which significantly differed patients with spontaneous HCV clearance and subjects with persistent HCV infection and could be used as explanatory variables for HCV outcome. Epistatic interactions between tested PON1 SNVs and IFNL4 rs368234815 were analyzed by the multifactor dimensionality reduction method.

Results

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 resolution than the genotypes composed of at least one more frequent allele. The most common haplotype, rs662A_rs854560A, was inversely associated with spontaneous HCV clearance. Compared to this haplotype, the rs662G_rs854560T indicated a 5.09-fold (95% CI 0.99 – 26.2, P = 0.032) higher chance for HCV resolution. The closest to significance was the epistatic gene-gene interaction between PON1 rs662, PON1 rs854560, and IFNL4 rs368234815 (P = 0.094). Regression model, including the PON1 rs662 GG genotype, the PON1 rs705379 TT 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 elimination were the IFNL4 rs368234815 TT/TT genotype (HR 2.841, 95% CI 1.434 - 5.625, P = 0.003) and RRT duration (HR 0.946, 95% CI 0.897 – 0.998, P = 0.042). The PON1 rs662 GG genotype provided P-value of 0.053.

Conclusion

The PON1 rs662 and rs854560 variant allele homozygotes are associated with a higher frequency of spontaneous HCV clearance in HD patients in univariate analyses.