Sustained viral response and treatment-induced cytopenia correlate with SLCs and KLF12 genotypes in interferon/ribavirin-treated Chinese chronic hepatitis C patients.

Abstract

BACKGROUND AND AIM:

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.

CONCLUSION:

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: Ruqi Mei, Xiumei Chi, Ruihong Wu, Hongqin Xu, Xiaomei Wang, Xiuzhu Gao, Haibo Sun, Juan Lv, Ge Yu, Fei Kong, Jing Jiang, Bing Sun, Jin Zhong, Yu Pan, Junqi Niu
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 31 Issue 8 Pg. 1489-97 (Aug 2016) ISSN: 1440-1746 [Electronic] Australia
• PMID: 26750805 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Anion Transport Proteins
• Antiporters
• Antiviral Agents
• Equilibrative Nucleoside Transporter 1
• Interferon alpha-2
• Interferon-alpha
• KLF12 protein, human
• Kruppel-Like Transcription Factors
• Recombinant Proteins
• SLC29A1 protein, human
• SLC4A11 protein, human
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b

Topics

• Adult
• Anion Transport Proteins (genetics)
• Antiporters (genetics)
• Antiviral Agents (adverse effects)
• China
• Drug Therapy, Combination
• Equilibrative Nucleoside Transporter 1 (genetics)
• Female
• Genetic Predisposition to Disease
• Hepacivirus (drug effects, pathogenicity)
• Hepatitis C, Chronic (diagnosis, drug therapy, genetics, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects)
• Kruppel-Like Transcription Factors (genetics)
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Pharmacogenomic Variants
• Polyethylene Glycols (adverse effects)
• Polymorphism, Single Nucleotide
• Recombinant Proteins (adverse effects)
• Retrospective Studies
• Ribavirin (adverse effects)
• Risk Factors
• Sustained Virologic Response
• Thrombocytopenia (chemically induced, diagnosis, genetics)
• Time Factors
• Treatment Outcome