BMJ open gastroenterology · 2015
Novel host genetic variations associated with spontaneous clearance of a single-source outbreak of HCV1b infections.
СтатьяНазвание и аннотация: Перевод в очереди
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You Hong, Liu Sandu, Xie Yong, Cong Rui, Sun Yameng, Ren Jingjing, Wei Kangfei, Jin Xin, Shi Yujian, Zhang Haiying, Li Jie, Wei Lai, Zhuang Hui, Cheng Mingliang, Jia Jidong
Аннотация
BACKGROUND AND AIMS: A total of 105 patients were identified as accidentally infected with hepatitis C virus genotype 1b (HCV1b) through blood transfusion from a single blood donor. This group provides a unique patient population to study host factors involved in the spontaneous clearance of HCV and disease progression.
METHODS: Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance.
RESULTS: Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9-12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10(-5)).
CONCLUSIONS: Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance.
METHODS: Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance.
RESULTS: Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9-12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10(-5)).
CONCLUSIONS: Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance.