Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females.
Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females.
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DOI：
10.1016/j.meegid.2014.07.034
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
M. Yue;Chunfang Gao;Jia-jia Wang;C. Wang;Le Feng;Jie Wang;R. Yu;Z. Peng;Xing-xin Xue;L. Cai;Nai-jun Fan;Yun Zhang;X. Deng
中科院分区：
文献类型：
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作者：
M. Yue;Chunfang Gao;Jia-jia Wang;C. Wang;Le Feng;Jie Wang;R. Yu;Z. Peng;Xing-xin Xue;L. Cai;Nai-jun Fan;Yun Zhang;X. Deng
Toll样受体7（TLR 7）在HCV感染中激发免疫应答中起着至关重要的作用。本研究旨在探讨TLR 7基因rs 179009、rs 179010和rs 179012单核苷酸多态性（single nucleotide polymorphisms，SNPs）对中国人群HCV感染预后的影响。共有1767名中国汉族人入组。评估了具有不同HCV感染结局的三组人群中SNP频率的分布，包括健康对照组、自发清除病例和病毒持续存在病例。然后在体外测定TLR 7激动剂咪喹莫特刺激后TLR 7 mRNA表达及IFN-α和IL-6的产生。结果表明，rs 179009 GG基因型与女性HCV感染易感性显著相关（OR = 2.42，95%CI = 1.24- 4.71，P = 0.01）。与ACG单倍型相比，女性单倍型GCG与HCV易感性显著相关（OR = 1.50，95%CI = 1.11- 2.03，P = 0.01）。在rs 179009基因功能研究中，GG基因型IFN-α水平低于AA基因型（P= 0.032）。我们的数据表明，TLR 7 rs 179009 GG基因型和单倍型GCG与中国女性HCV感染的易感性增加有关，这可能是由于IFN-α反应受损所致。
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) ofTLR7, 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. ThenTLR7mRNA expression and the production of IFN-α and IL-6 after TLR7 agonist Imiquimod stimulationin vitrowere 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 thatTLR7rs179009 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.