Association of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) polymorphisms with susceptibility and disease progression of HBV infection.
Association of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) polymorphisms with susceptibility and disease progression of HBV infection.
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T 细胞免疫球蛋白和粘蛋白结构域分子 3 (Tim-3) 多态性与 HBV 感染的易感性和疾病进展的关系
DOI：
10.1371/journal.pone.0098280
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Liao J;Zhang Q;Liao Y;Cai B;Chen J;Li L;Wang L
含T细胞免疫球蛋白及黏蛋白结构域分子3（Tim - 3）在乙型肝炎病毒（HBV）感染和肝细胞癌（HCC）中对T细胞的调节起着重要作用。然而，鲜有研究报道Tim - 3基因变异与HBV感染易感性及病情进展的关联。在本研究中，我们聚焦于Tim - 3基因多态性与HBV感染、乙肝表面抗原（HBsAg）血清学清除及肝细胞癌之间的关系。
本研究共纳入800名研究对象。在此研究了四组人群，包括HBV感染者、HBsAg血清学清除者、HBV相关肝细胞癌患者以及健康对照者。对Tim - 3的三个单核苷酸多态性（SNP）位点，即rs246871、rs25855和rs31223进行基因分型，以分析Tim - 3基因多态性与HBV感染易感性及疾病进展的关系。
我们的研究发现，rs31223和rs246871与HBV感染的疾病进展相关，而这三个SNP位点均与HBV易感性无关。研究发现rs31223的次要等位基因“C”与HBsAg血清学清除概率增加相关（P = 0.033），rs246871的基因型“CC”与HBV相关肝细胞癌发生概率增加相关（P = 0.007）。与此一致的是，对这三个多态性位点的单倍型分析也显示，单倍型模块CGC*和TGC*与HBsAg血清学清除显著相关（P < 0.05），而单倍型模块CAT*、CGT*、TAC*和TGT*与HBV相关肝细胞癌显著相关（所有P均 < 0.05）。
Tim - 3基因变异对HBV感染的疾病进展有重要影响。携带特定Tim - 3基因多态性的HBV感染者有可能发生肝细胞癌或出现HBsAg血清学清除。
Purpose T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma. Methods A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection. Results Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele “C” of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033) and genotype “CC” of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05). Conclusions Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance.
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TIM-3 表达是肿瘤组织中调节性 T 细胞的特征，并与肺癌进展相关
影响因子：
3.7
作者：
Gao X;Zhu Y;Li G;Huang H;Zhang G;Wang F;Sun J;Yang Q;Zhang X;Lu B
通讯作者：
Lu B
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
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影响因子：
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作者：
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发表时间：
2006-06-12
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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Hafler DA
影响因子：
30.5
作者：
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影响因子：
24.1
作者：
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