Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Gene. 2013 Oct 10;528(2):132-8. doi: 10.1016/j.gene.2013.07.036. Epub 2013 Jul 31.
MicroRNAs (miRNAs) regulate posttranscriptional gene expression usually by binding to 3'-untranslated regions (3'UTRs) of target message RNAs (mRNAs). Previous studies have demonstrated that SNPs within miRNA target sites could modulate miRNA-mRNA interaction to affect the regulation of target genes and the individual's diseases. So far, little is known about the relationship of miRNA binding site polymorphisms with the risk of metabolic syndrome (MetS) in the general population. Therefore, we conducted a case-control study in Chinese Han population to evaluate the association between SNPs within miRNA binding sites and risk of MetS. 8 SNPs in miRNA binding sites with a minor allele frequency (MAF) of ≥ 0.05 in the Chinese Han population were selected by bioinformatics software. TaqMan ®assay was performed to test the genotypes in MetS patients (n=1026) and normal controls (n=1032). We found rs5750146 (adjusted odds ratio (OR)=1.24 for GA/AA, P=0.023, compared with GG), rs5999924 (adjusted OR=1.22 for AT/TT, P=0.038, compared with AA) in the APOL6 3'UTR were identified to correlate with MetS in the total sample and females. Rs11724758 (adjusted OR=0.65 for AA, P=0.002, compared with GG) in the FABP2 3'UTR was found to correlate with MetS in the total sample and males. Correlations between FABP2 rs11724758 polymorphisms and components of MetS reveal that high-density lipoprotein cholesterol (HDL-c) levels are significantly higher in FABP2 rs11724758 AA genotype carrier compared with noncarriers, whereas triglycerides (TG) and fasting plasma glucose (FG) were to be significantly lower in the AA genotype carrier. These findings indicate that these three polymorphisms which located at the predicted miRNAs binding sites were identified to contribute to susceptibility to MetS in the Chinese Han population.
微小 RNA（miRNA）通常通过与靶信使 RNA（mRNA）的 3'非翻译区（3'UTR）结合来调节转录后基因表达。先前的研究表明，miRNA 靶位点内的 SNP 可以调节 miRNA-mRNA 相互作用，从而影响靶基因的调控和个体疾病。到目前为止，关于 miRNA 结合位点多态性与一般人群代谢综合征（MetS）风险的关系知之甚少。因此，我们在中国汉族人群中进行了病例对照研究，以评估 miRNA 结合位点 SNP 与 MetS 风险之间的关系。通过生物信息学软件选择 miRNA 结合位点中在汉族人群中 minor allele frequency（MAF）≥0.05 的 8 个 SNP。采用 TaqMan®assay 检测 MetS 患者（n=1026）和正常对照（n=1032）的基因型。我们发现，APOL6 3'UTR 中的 rs5750146（GA/AA 调整后的比值比（OR）=1.24，P=0.023，与 GG 相比）和 rs5999924（AT/TT 调整后的 OR=1.22，P=0.038，与 AA 相比）与总样本和女性中的 MetS 相关。在 FABP2 3'UTR 中发现 rs11724758（AA 调整后的 OR=0.65，P=0.002，与 GG 相比）与总样本和男性中的 MetS 相关。FABP2 rs11724758 多态性与 MetS 成分的相关性表明，与非携带者相比，FABP2 rs11724758 AA 基因型携带者的高密度脂蛋白胆固醇（HDL-c）水平显著升高，而甘油三酯（TG）和空腹血糖（FG）水平显著降低。这些发现表明，这三个位于预测 miRNA 结合位点的多态性被确定为中国汉族人群中 MetS 易感性的贡献因素。
