Abstract
A recent genome-wide association study (GWAS) has identified the single-nucleotide polymorphism (SNP) rs4273729 in a 100-kbp region comprising human leukocyte antigens (HLAs) class II genes as an important predictor of hepatitis C virus (HCV) clearance in European and African populations. This study was to determine whether this polymorphism is also associated with spontaneous HCV clearance as well as response to interferon treatment in Chinese patients. Thus, 686 chronic HCV carriers, 432 individuals with spontaneous viral clearance and 243 patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment were genotyped. The rs4273729 GG genotype was strongly associated with spontaneous HCV clearance as well as better IFN/RBV treatment response compared with the GC/CC genotypes in Chinese Han population (additive model: odds ratio (OR)=0.62, 95% confidence interval (95% CI)=0.51–0.76; OR=0.58, 95% CI=0.38–0.88, respectively). Rs4273729, rs12980275, baseline HCV RNA and platelet level were independent predictors for sustained virological response (SVR). The area under the receiver-operating characteristic curve (AUC) was 0.578 when including rs4273729 alone, but the prediction value was improved significantly (AUC=0.733) when further including rs12980275, baseline viral load and baseline platelet level. In conclusion, the genetic variation of rs4273729 is associated with clearance of HCV in both the natural course and the treatment process in Chinese Han population.
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Acknowledgements
The current study was supported in part by National Natural Science Foundation of China (Nos. 81473029, 81502853, 81273146 and 81473028), Research and Innovation Project for College Graduates of Jiangsu Province of China (KYZZ_0265), Natural Science Foundation of Jiangsu Province (BK20151026), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Medical Reform Project of Health and Family Planning Commission of Jiangsu Province of China (YG201413), Science and Technology Program of Zhenjiang, China (SH20141) and Tianqing Liver Disease Research Supporting Foundation of China Hepatitis Foundation (TQGB20140014). We thank the students who have worked on the study, including Yuangyuan Zhang, Hui Zheng, Wenzhe Ma, Wenjuan Zhang and Xuecheng Song. We also thank the doctors and the nurses from the Jurong Peoples’s Hospital for helping with sample collection and organization of the field investigation. This research would not have been possible without the consent and help of the participants.
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Xu, Y., Huang, P., Yue, M. et al. A novel polymorphism near HLA class II region is associated with spontaneous clearance of HCV and response to interferon treatment in Chinese patients. J Hum Genet 61, 301–305 (2016). https://doi.org/10.1038/jhg.2015.145
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DOI: https://doi.org/10.1038/jhg.2015.145
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