miR-499 rs3746444位点多态性与肝细胞癌 发病风险的关系  

Relationship between miR-499 rs3746444 polymorphism and risk of hepatocellular carcinoma

作　　者：韦琴 黄冰 余红平 秦林原 于祥远 WEI Qin;HUANG Bing;YU Hongping;QIN Linyuan;YU Xiangyuan(Guilin Medical University,Guilin 541100,China)

机构地区：[1]桂林医学院公共卫生学院,广西桂林541100 [2]广西医科大学附属肿瘤医院

出　　处：《山东医药》2021年第10期16-20,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81660567);广西自然科学基金资助项目(2020GXNSFAA238025、2015GXNSFCB139007)。

摘　　要：目的系统评价微小RNA-499(miR-499)rs3746444位点多态性与肝细胞癌(HCC)发病风险的关系。方法计算机检索Web of science、PubMed、中国知网、万方数据库中公开发表的关于miR-499 rs3746444位点多态性与HCC发病风险关系的病例对照研究,采用Stata12.0统计软件进行Meta分析。结果本研究共纳入18篇文献,其中高质量文献11篇、中等质量文献7篇,纳入HCC患者4433例(病例组)、健康志愿者5686例(对照组)。Meta整组分析显示,miR-499 rs3746444位点多态性与HCC遗传易感性无明显相关性(P均>0.05),其中等位基因模型、显性遗传模型、杂合子模型合并的优势比(OR)分别为1.14(95%CI:0.97~1.33)、1.16(95%CI:0.99~1.38)、0.87(95%CI:0.74~1.02)。以基因分型方法(PCR-RFLP、其他)、病例组样本量(n>200、n≤200)以及是否符合HWE(符合、不符合)进行亚组分析,结果发现miR-499 rs3746444位点多态性与HCC遗传易感性显著相关(P均<0.05)。在等位基因模型下,与A等位基因比较,G等位基因可显著增加病例组n>200、其他基因分型方法以及符合HWE亚组个体罹患HCC的风险[OR及其95%CI分别为1.19(1.06~1.35)、1.34(1.09~1.66)、1.32(1.01~1.72)];在显性遗传模型下,与AA基因型比较,GG+AG基因型可显著增加病例组n>200、其他基因分型方法亚组个体罹患HCC的风险[OR及其95%CI分别为1.22(1.05~1.43)、1.49(1.16~1.92)];在杂合子模型下,与AA基因型比较,AG基因型可显著增加病例组n>200、其他基因分型方法亚组个体罹患HCC的风险[OR及其95%CI分别为1.20(1.01~1.42)、1.55(1.25~1.92)]。Begg′s检验显示,不同基因模型下纳入文献的漏斗图基本呈对称分布(P均>0.05);Egger′s检验显示,不同基因模型下未发现存在发表偏倚(P均>0.05)。敏感性分析未发现总体效应的OR及其95%CI因单篇文献剔除而出现明显波动,研究结果的稳健性较好。结论miR-499 rs3746444位点多态性与HCC的发病风险显著相关,此关联仅存在于病例�Objective To systematically evaluate the relationship between the miR-499 rs3746444 polymorphism and the onset of hepatocellular carcinoma(HCC).Methods The case-control studies on relationship between miR-499 rs3746444 polymorphism and HCC risk were retrieved from Web of Science,PubMed,CNKI,and Wanfang,and we used Stata12.0 statistical software for the meta-analysis.Results A total of 18 case-control studies were included,including 11 high-quality studies and 7 medium-quality studies with 4433 HCC patients(case group)and 5686 healthy volunteers(control group).The overall meta-analysis showed no significant association between miR-499 rs3746444 polymorphisms and HCC genetic susceptibility(all P>0.05);among them,the OR and 95%CI of allele model,dominant model,and het⁃erozygous model were 1.14(0.97-1.33),1.16(0.99-1.38),and 0.87(0.74-1.02),respectively.According to the ge⁃notyping method(PCR-RFLP,others),the sample size of the case group(n>200,n≤200),and HWE(conformity,nonconformity),the subgroup analysis was performed,which showed that miR-499 rs3746444 polymorphism was significantly correlated with the HCC genetic susceptibility(P<0.05).Under the allele model,compared with the A allele,the G allele significantly increased the HCC risk in the subgroups of the case group with sample size>200,other genotyping meth⁃ods,and being in conformity with HWE[OR and 95%CI were 1.19(1.06-1.35),1.34(1.09-1.66),and 1.32(1.01-1.72),respectively].Under the dominant model,compared with the AA genotype,the GG+AG genotype significantly increased the HCC risk in the subgroups of the case group with sample size>200 and other genotyping methods[OR and 95%CI were 1.22(1.05-1.43)and 1.49(1.16-1.92),respectively].Under the heterozygous model,compared with the AA genotype,the AG genotype significantly increased the HCC risk in the subgroups of the case group with a sample size>200 and other genotyping methods[OR and 95%CI were 1.20(1.01-1.42)and 1.55(1.25-1.92),respectively].The Begg's test showed that the funnel plots of the includ

关 键 词：肝细胞癌 微小RNA-499 单核苷酸多态性 发病风险 关联研究 

分 类 号：R735.7[医药卫生—肿瘤]