对血液透析个体中丙型肝炎病毒（HCV）自发清除相关的对氧磷酶 1 基因（PON1）变异：一项病例对照研究。
Paraoxonase 1 gene (PON1) variants concerning hepatitis C virus (HCV) spontaneous clearance in hemodialysis individuals: a case-control study.
机构信息
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-781, Poznań, Wielkopolska, Poland.
Department of Ophthalmology and Optometry, Poznan University of Medical Sciences, 60-806, Poznań, Wielkopolska, Poland.
出版信息
BMC Infect Dis. 2021 Aug 26;21(1):875. doi: 10.1186/s12879-021-06597-4.
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.
背景
探讨 PON1 rs854560、rs662、rs705379、rs368234815 单核苷酸变异与 HCV 清除率之间的关联，以及在血液透析患者中这些 PON1 单核苷酸变异与干扰素-λ4 基因（IFNL4）rs368234815 变异之间的相互作用。
方法
本研究纳入了 83 例自发性清除 HCV 的血液透析患者（均已知 IFNL4 rs368234815 变异）和 104 例 HCV RNA 持续阳性的血液透析患者（102 例成功进行了 IFNL4 rs368234815 变异基因分型）。我们通过高分辨率熔解曲线分析（rs662）或预设计的 TaqMan 单核苷酸变异基因分型检测（rs854560、rs705379）对 PON1 进行基因分型。我们使用逻辑回归模型，在调整临床混杂变量的情况下，评估遗传数据与 HCV 结局之间的关联。采用多因素维度缩减方法分析了测试的 PON1 单核苷酸变异与 IFNL4 rs368234815 之间的上位性相互作用。
结果
在隐性遗传模型中，PON1 rs662 GG（OR 9.94，95%CI 1.20-82.7，P=0.022）和 rs854560 TT（OR 4.31，95%CI 1.62-11.5，P=0.003）基因型与 HCV 清除率较高有关。由 rs662A_rs854560A_rs705379 组成的单倍型与自发性 HCV 清除无关。IFNL4 rs368234815 TT/TT 变异在携带不同 PON1 单核苷酸变异的个体中分布均匀。基因-基因上位性分析未发现测试的 PON1 单核苷酸变异与 IFNL4 rs368234815 之间的相互作用（P=0.094）。回归模型包括 PON1 rs662 GG 基因型、PON1 rs854560 基因型、IFNL4 rs368234815 TT/TT 基因型、RRT 起始年龄、RRT 持续时间和慢性肾小球肾炎作为自发性 HCV 清除的可能解释变量，结果表明自发性 HCV 清除的显著预测因子为 IFNL4 rs368234815 TT/TT 基因型（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）和 RRT 持续时间（OR 0.930，95%CI 0.879-0.984，P=0.011）。
结论
在血液透析患者中，PON1 rs662 GG 和 rs854560 TT 与自发性 HCV 清除率较高有关。
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