title: Genetic variation in NOS2A is associated with a sustained virological response to peginterferon plus ribavirin therapy for chronic hepatitis C in Taiwanese Chinese.
abstract: This study aimed to evaluate whether genetic polymorphisms of the inducible nitric oxide synthase (iNOS) gene NOS2A could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and two single nucleotide polymorphisms (SNPs) in NOS2A. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without a SVR. Among the NOS2A SNPs examined, the combination of genotypes A/A and A/G of rs2248814 was inversely correlated with SVR in patients infected with HCV-1 (P = 0.0048), particularly in males (P = 0.0281). This effect was not observed in patients infected with HCV-2. The AC NOS2A haplotype comprising two SNPs (rs2248814 and rs2072324) was found to be associated with SVR, and its presence may decrease the chances for a successful outcome of treatment of patients infected with HCV-1 (P = 0.0053). HCV-1 infected patients who carried the A-C diplotype will have a lower success rate of achieving a SVR (P = 0.0117). In addition, a multivariate logistic regression model for predicting a SVR revealed that the presence of the A-C diplotype interactively affected the outcome of PEG-IFNα-RBV treatment. The presence of NOS2A SNPs and the association with SVR showed that NOS2A polymorphisms may influence the therapeutic outcomes of patients infected with HCV-1 under standard of care treatment.
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Lim
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Liao
authors.forename: Dong-Zong
authors.initials: DZ
authors.lastname: Hung
authors.forename: Ni
authors.initials: N
authors.lastname: Tien
authors.forename: Cing-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Shih-Yu
authors.initials: SY
authors.lastname: Chang
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Chang
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C417083:peginterferon alfa-2b
keywords: hepatitis C virus; inducible nitric oxide synthase; standard of care treatment; sustained virological response