Genetic variations of IL-28B and PD-1 are in association with the susceptibility and outcomes of HCV infection in Southeast China.
Programmed cell death-1 (PD-1) is an important co-inhibitory molecule involved in the progression of chronic viral infections. To investigate the associations of three single nucleotide polymorphisms (SNPs) (rs10204525, rs2227982 and rs36084323) in PD-1 and a previously well-inquired SNP rs12979860 in IL-28B with the outcomes of hepatitis C virus (HCV) infection in Southeast China, a total of 375 healthy controls, 219 spontaneous resolved HCV patients and 600 chronic HCV patients were enrolled in this study. The generation of HCV F protein and PD-1 expression on T cells was determined. Multivariate logistic regression analysis showed no association of rs12979860 CC genotype with spontaneous clearance of HCV infection in our subjects. The generation of HCV F protein was significantly related to HCV infection chronicity, but no significant relationship was found between HCV F protein and SNPs in PD-1. The rs10204525 TT genotype was associated with an increased risk of HCV infection chronicity in age ⩽56years subgroup (adjusted OR=0.390, P=3.8×10(-4)). The C allele of rs10204525 played protective roles in females infected with HCV (adjusted OR=0.608, P=0.008). A significant higher percentage of PD-1 expression on T cells was observed in rs10204525 TT genotype when compared to CC genotype (P=0.047). Moreover, a significant genotype-genotype interaction between IL-28B rs12979860 CC and PD-1 rs10204525 TC+CC was found to be associated with higher rates of spontaneous clearance (adjusted OR=0.689, P=0.032). The combined effect of rs12979860 and rs10204525 was of great value in predicting the outcomes of HCV infection. These analyses showed the importance of IL-28B and PD-1 polymorphisms and their interactions in the outcomes of HCV infection in Chinese Han population in Southeast China.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: xiaowen2013cpu@163.com.
Wen
W
Xiao
Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
Qi
Q
Zhang
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Huadong Research Institute for Medicine and Biotechnics, Nanjing, China. Electronic address: dengxiaozhao1002@vip.sina.com.
Xiao Zhao
XZ
Deng
Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Long Feng
LF
Jiang
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
Dan Yan
DY
Zhu
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
Jia Ping
JP
Pei
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Mao Lei
ML
Xu
Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
Bing Jun
BJ
Li
Huadong Research Institute for Medicine and Biotechnics, Nanjing, China. Electronic address: science2008@hotmail.com.
Chang Jun
CJ
Wang
Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
Jing Hai
JH
Zhang
Department of Clinical Laboratory, Nanjing Second Hospital, Nanjing, China.
Zhen Xian
ZX
Zhou
Department of Clinical Laboratory, Yixing People's Hospital, Yixing, China.
Wei Liang
WL
Ding
Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
Xiao Dong
XD
Xu
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Ming
M
Yue
D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D060005:Genotyping Techniques; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000502:physiology; D012075:Remission, Spontaneous; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; D061026:Programmed Cell Death 1 Receptor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C105992:PDCD1 protein, human
Chronic HCV infection; IL-28B; PD-1; Polymorphism; Spontaneous clearance