microRNA-149和microRNA-499基因多态性与肝癌易感性的Meta分析

A meta-analysis of microRNA-149, microRNA-499 gene polymorphism and susceptibility to hepatocellular carcinoma

目的采用Meta分析方法探讨microRNA-149（rs2292832）和microRNA-499（rs3746444）位点多态性与肝癌易感性的关系。方法以“肝癌／肝细胞癌”、“miRNA．149／miR．149／microRNA-149”、“miRNA-499／miR-499／microRNA．499”、“hepatocellularcarcinoma”为检索词，检索中国学术期刊全文数据库、中国生物医学文献数据库、中国科技期刊全文数据库、万方知识服务平台、PubMed和WebofScience数据库，系统收集建库至2015年5月31日为止公开发表的有关rs2292832和rs3746444位点多态性与肝癌易感性病例．对照研究，提取数据进行Meta分析，计算合并OR（95％CI）值，并进行生物信息学分析。结果最终纳人13篇文献，携带rs2292832位点纳入5篇文献，携带rs3746444位点纳入12篇文献，其中携带rs2292832位点病例1096例，对照1701名；纳入携带rs3746444位点病例3117例，对照4126名。Meta分析结果显示，rs2292832和rs3746444位点多态性与肝癌易感性无相关性，等位基因的0R（95％CI）值分别为0．99（0．78-1．28）和1．11（0．88-1．40）。分层结果显示，病例组和对照组总调查对象〉400名或采用两种不同基因分型方法的研究，rs3746444位点多态性与肝癌易感性存在相关性，其C等位基因可能是肝癌易感性基因，0R（95％C1）值分别为1．32（1．02—1．70）和1．34（1．09—1．66）。生物信息学分析结果显示，rs2292832和rs3746444位点在肝癌细胞中的基因表达水平降低，提示2个位点均可能影响基因转录。Cochran’s Q检验结果显示，rs2292832和rs3746444位点所纳入的文献异质性均较大（I2值分别为0．78和0．84，P值均〈0．10）。结论rs2292832和rs3746444位点多态性与肝癌易感性均无相关性；但分层结果提示rs3746444等位基因C可能与肝癌易感性相关；生物信息学分析提示本研究的2个位点可能影响基因转录。

Objective To investigate the relationship between mieroRNA-149 （rs2292832）, microRNA-499 （rs2292832） polymorphism and hepatocellular carcinoma susceptibility by meta-analysis. Methods We used ＂hepatocellular carcinoma/HCC＂, ＂miRNA-149/miR-149/microRNA-149＂, and ＂miRNA-499/miR-499/microRNA-499＂ as key words to search papers in databases including China National Knowledge Interact （CNKI）, Chinese BioMedical Literature （CBM）, Vip Citation Databases （VIP）, Wanfang, PubMed and Web of Science databases, and collected the case-control studies on the association of rs2292832 or rs3746444 and the susceptibility to hepatocellular carcinoma from updated to May 3lst 2015. Data were extracted by two independent reviewers and pooled OR with 95% CI was calculated. A bioinformatics analysis was further conducted. Results A total of 13 research papers were collected, and 5 studies for rs2292832 and 12 studies for rs3746444, l 096 cases and 1 701 controls were included for rs2292832 and 3 117 cases and 4 126 controls were included for rs3746444. Meta-analysis failed to detect associations between rs2292832, rs3746444 and susceptibility to hepatoeellular carcinoma under each genetic model tested and alleles of 0R（95% CI） were 0.99（0.78-1.28） and 1.11（0.88-1.40）. However, subgroup analysis showed that rs3746444 C allele seem to be associated with an increased hepatoeellular carcinoma risk in both researches which had more than 400 samples and which used more accurate genotyping methods, and 0R（95%CI） were 1.32（1.02-1.70） and 1.34（1.09-1.66）, respectively. Furthermore, hioinformaties analysis also showed that the expression of both SNPs were down-regulated in HepG2 cells and indicated possible functional effects on gene transcription. Coehran＇s Q test indicated that there was the heterogeneity among the studies included. Conclusions No significant association was found between rs2292832, rs3746444 and susceptibility to hepatocellular carcinoma, but subgroup study indicated C allele might be associated with increased hepatocellular carcinoma risk for rs3746444. Bioinformaties analysis indicated that the two SNPs might have possible influence on gene transcription.