功能性miR-146a、miR-149、miR-196a2和miR-499基因多态性与肝细胞癌易感性：一项更新的荟萃分析。
Functional miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms and the susceptibility to hepatocellular carcinoma: An updated meta-analysis.
作者信息
Zheng Lei, Zhuang Chunbo, Zhao Junwei, Ming Liang
机构信息
Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian She East Road, Zhengzhou, Henan, PR China.
Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian She East Road, Zhengzhou, Henan, PR China; Key Clinical laboratory of Henan Province, PR China.
出版信息
Clin Res Hepatol Gastroenterol. 2017 Dec;41(6):664-676. doi: 10.1016/j.clinre.2017.03.005. Epub 2017 May 9.
OBJECTIVE
Single nucleotide polymorphisms of miRNAs play important roles in the pathogenesis of hepatocellular carcinoma (HCC). To evaluate the association between four common miRNAs (miR-146a rs2910164; miR-149 rs2292832; miR-196a2 rs11614913 and miR-499 rs3746444) and HCC risk, an updated meta-analysis was performed.
METHODS
32 studies including 12,405 HCC cases and 15,056 controls were used for this meta-analysis. There were 22 studies with 7894 cases and 10,221 controls for miR-146a, 9 studies with 2684 HCC cases and 3464 controls for miR-149, 17 studies with 6937 cases and 8217 controls for miR-196a2 and 16 studies with 4158 cases and 5264 controls for miR-499. Odds radios (ORs) and 95% confidence intervals (CIs) were used to assess the HCC risk.
RESULTS
Meta-analysis showed that miR-146a was associated with HCC risk under the heterozygote model (OR=1.10, 95%CI=1.03-1.17, P=0.007), whereas no association was found in Caucasian using all genetic models. For miR-196a2 polymorphism, an increased risk of HCC was observed based on four models (C vs T: OR=1.15, 95%CI=1.05-1.26, P=0.003; CC vs TT: OR=1.35, 95%CI=1.12-1.63, P=0.002; CC+CT vs TT: OR=1.20, 95%CI=1.04-1.37, P=0.01 and CC vs CT+TT: OR=1.23, 95%CI=1.06-1.42, P=0.006). Association of miR-499 with HCC risk was only detected in the subgroup of studies which did not use polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) under the allelic, heterozygote and dominant models. However, negative results were obtained for the association of miR-149 and HCC susceptibility.
CONCLUSION
Our results suggest that miR-146a and miR-196a2 polymorphisms are associated with increased risk of HCC, especially in Asian.
目的
微小RNA（miRNA）的单核苷酸多态性在肝细胞癌（HCC）的发病机制中起重要作用。为评估四种常见miRNA（miR-146a rs2910164；miR-149 rs2292832；miR-196a2 rs11614913和miR-499 rs3746444）与HCC风险之间的关联，进行了一项更新的荟萃分析。
方法
本荟萃分析使用了32项研究，包括12405例HCC病例和15056例对照。其中，22项研究包含7894例病例和10221例对照用于miR-146a分析，9项研究包含2684例HCC病例和3464例对照用于miR-149分析，17项研究包含6937例病例和8217例对照用于miR-196a2分析，16项研究包含4158例病例和5264例对照用于miR-499分析。采用比值比（OR）和95%置信区间（CI）评估HCC风险。
结果
荟萃分析表明，在杂合子模型下miR-146a与HCC风险相关（OR = 1.10，95%CI = 1.03 - 1.17，P = 0.007），而在所有遗传模型下白种人中未发现关联。对于miR-196a2多态性，基于四种模型观察到HCC风险增加（C与T：OR = 1.15，95%CI = 1.05 - 1.26，P = 0.003；CC与TT：OR = 1.35，95%CI = 1.12 - 1.63，P = 0.002；CC + CT与TT：OR = 1.20，95%CI = 1.04 - 1.37，P = 0.01；CC与CT + TT：OR = 1.23，95%CI = 1.06 - 1.42，P = 0.006）。仅在未使用聚合酶链反应和限制性片段长度多态性（PCR - RFLP）的研究亚组中，在等位基因、杂合子和显性模型下检测到miR-499与HCC风险的关联。然而，miR-149与HCC易感性的关联结果为阴性。
结论
我们的结果表明，miR-146a和miR-196a2多态性与HCC风险增加相关，尤其是在亚洲人群中。
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