title: Sustained viral response and treatment-induced cytopenia correlate with SLCs and KLF12 genotypes in interferon/ribavirin-treated Chinese chronic hepatitis C patients.
abstract: OBJECTIVE
  Genetic variations in solute carrier (SLC) genes are associated with liver diseases, and Kruppel-like factor 12 (KLF12) affects the b chain of hemoglobin. We investigated possible correlations of SLC and KLF12 polymorphisms with viral clearance (spontaneous and treatment-induced) and adverse effects in Chinese chronic hepatitis C (CHC) patients.
  
  
  METHODS
  We genotyped the single nucleotide polymorphisms in 525 CHC patients, 137 patients with spontaneous clearance, and 207 healthy controls. Three hundred fifty-seven CHC patients received recombinant interferon-alpha2b/ribavirin (IFN-α2b/RBV) treatment, and 175 patients were chosen for analysis of drug-induced cytopenia. All raw P-values were corrected by the Bonferroni method.
  
  
  RESULTS
  A higher rate of sustained viral response was detected in patients with SLC4A11 rs3810560 CC variant versus TT/TC variant (76.9% vs 59.2%; OR, 2.42; 95% CI, 1.06-5.56, P = 0.037 after adjustment), but there was no significant difference among different hepatitis C virus genotypes. RBV-induced anemia was independently correlated with SLC29A1 rs760370 AA genotype (OR, 2.90; 95% CI, 1.29-6.54, P = 0.010), and the severity of IFN-induced thrombocytopenia was related to GG genotype (OR, 4.98; 95% CI, 1.27-19.61; P = 0.021); the detected effects held true for HCV-2a patients but weakened in HCV-1b patients. A reactive increase in platelet count was closely associated with KLF12 rs9543524 TT variant.
  
  
  CONCLUSIONS
  SLC4A11 rs3810560 polymorphism independently affected the sustained viral response rates in CHC patients, whereas SLC29A1 rs760370 and KLF12 rs9543524 single nucleotide polymorphisms correlated with treatment-induced adverse events. Clearly, the predictive power varied with HCV genotypes and the reason for genotype-dependent discrepancy was not fully understood.
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Ruqi
authors.initials: R
authors.lastname: Mei
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Xiuzhu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.affiliation: Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
mesh_terms: D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D000998:Antiviral Agents / Q000009:adverse effects*; D002681:China; D004359:Drug Therapy, Combination; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D000071184:Pharmacogenomic Variants; D011092:Polyethylene Glycols / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000009:adverse effects; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects*; D012307:Risk Factors; D000072230:Sustained Virologic Response; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D000998:Antiviral Agents; D033721:Equilibrative Nucleoside Transporter 1; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D011994:Recombinant Proteins; C438649:SLC29A1 protein, human; C425809:SLC4A11 protein, human; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b
keywords: Kruppel-like factor 12; adverse event; anemia; chronic hepatitis C; polymorphism; solute carrier; treatment outcome