title: Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females.
abstract: Toll-like receptors 7 (TLR7) play a crucial role in provoking an immune response in HCV infection. We aimed to investigate whether single nucleotide polymorphisms (SNPs) of TLR7, including rs179009, rs179010 and rs179012, affect the outcomes of HCV infection among the Chinese population. A total of 1767 Chinese Han individuals were enrolled. The distribution of SNP frequencies among three groups with different outcomes of HCV infection was assessed, including healthy controls, cases with spontaneous clearance and cases with viral persistence. Then TLR7 mRNA expression and the production of IFN-α and IL-6 after TLR7 agonist Imiquimod stimulation in vitro were determined. Our results suggested that rs179009 GG genotype was significantly associated with a higher risk of the susceptibility to HCV infection among female subjects (OR=2.42, 95% CI=1.24-4.71, P=0.01). Haplotype GCG was significantly associated with a high risk for HCV susceptibility (OR=1.50, 95% CI=1.11-2.03, P=0.01) as compared with the reference haplotype ACG among females. In the functional research of rs179009, a lower IFN-α level was observed in GG genotype than in AA genotype (P=0.032). Our data indicate that TLR7 rs179009 GG genotype and haplotype GCG were associated with an increased risk of the susceptibility to HCV infection among Chinese females, which may be due to the impaired IFN-α response.
authors.affiliation: School of Life Science and Technology, Jiangsu Province Hospital, No. 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China; Huadong Research Institute for Medicine and Biotechnics, No. 293 Zhongshan East Road, Nanjing 210002, Jiangsu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Anal-Colorectal Surgery, The 150th Central Hospital of Chinese People's Liberation Army, No. 2 Huaxia West Road, Jianxi District, Luoyang 471031, Henan, China.
authors.forename: Chun-fang
authors.initials: CF
authors.lastname: Gao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Jia-jia
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293 Zhongshan East Road, Nanjing 210002, Jiangsu, China.
authors.forename: Chang-jun
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Infection and Immunity, Yixing People's Hospital, No. 75 Tongzhenguan Road, Yixing 214200, Jiangsu, China.
authors.forename: Le
authors.initials: L
authors.lastname: Feng
authors.affiliation: School of Nursing, Nanjing Medical University, No. 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Rong-bin
authors.initials: RB
authors.lastname: Yu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Zhi-hang
authors.initials: ZH
authors.lastname: Peng
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Xing-xin
authors.initials: XX
authors.lastname: Xue
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Anal-Colorectal Surgery, The 150th Central Hospital of Chinese People's Liberation Army, No. 2 Huaxia West Road, Jianxi District, Luoyang 471031, Henan, China.
authors.forename: Nai-jun
authors.initials: NJ
authors.lastname: Fan
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293 Zhongshan East Road, Nanjing 210002, Jiangsu, China; Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 818 East Tianyuan Road, Nanjing 211166, Jiangsu, China. Electronic address: zhangyunvip@126.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293 Zhongshan East Road, Nanjing 210002, Jiangsu, China. Electronic address: dengxiaozhao1002@vip.sina.com.
authors.forename: Xiao-zhao
authors.initials: XZ
authors.lastname: Deng
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D016174:Hepacivirus; D006526:Hepatitis C / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D063868:Patient Outcome Assessment; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D051199:Toll-Like Receptor 7 / Q000235:genetics*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051199:Toll-Like Receptor 7
keywords: Hepatitis C virus; Outcome; Single nucleotide polymorphism; Susceptibility; Toll-like receptor 7