OBJECTIVE MicroRNAs (miRNAs) play an important role in posttranscriptional regulation by binding to target sites in the 3'UTR of protein-coding genes. Genetic variation within target sites may potentially disrupt the binding activity of miRNAs, thereby impacting this regulation. In the current study, we investigated whether any established BMI-associated genetic variants potentially function by altering a miRNA target site. METHODS The genomic positions of all predicted miRNA target site seed regions were identified, and these positions were queried in the T2D Knowledge Portal for variants that associated with BMI in the GIANT UK Biobank. This in silico analysis identified ten target site variants that associated with BMI with a P value ≤ 5 × 10-8. These ten variants mapped to nine genes, FAIM2, CCDC171, ADPGK, ZNF654, MLXIP, NT5C2, SHISA4, SLC25A22, and CTNNB1. RESULTS In vitro functional analyses showed that five of these target site variants, rs7132908 (FAIM2), rs4963153 (SLC25A22), rs9460 (ADPGK), rs11191548 (NT5C2), and rs3008747 (CCDC171), disrupted the binding activity of miRNAs to their target in an allele-specific manner. CONCLUSION In conclusion, our study suggests that some established variants for BMI may function by altering miRNA binding to a 3'UTR target site.

中文翻译：

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已建立的 BMI 基因的潜在 miRNA 靶位点中遗传变异的鉴定和功能验证。

目的 MicroRNAs (miRNAs) 通过与蛋白质编码基因 3'UTR 中的靶位点结合，在转录后调控中发挥重要作用。靶位点内的遗传变异可能会破坏 miRNA 的结合活性，从而影响这种调节。在目前的研究中，我们调查了任何已建立的 BMI 相关遗传变异是否可能通过改变 miRNA 靶位点发挥作用。方法 确定所有预测的 miRNA 靶位点种子区域的基因组位置，并在 T2D 知识门户中查询这些位置，以获取与 GIANT UK Biobank 中的 BMI 相关的变异。该计算机分析确定了 10 个与 BMI 相关的目标位点变异，P 值≤ 5 × 10-8。这十个变异映射到九个基因，FAIM2、CCDC171、ADPGK、ZNF654、MLXIP、NT5C2、SHISA4、SLC25A22 和 CTNNB1。结果 体外功能分析表明，这些靶位点变体中的 5 个，rs7132908 (FAIM2)、rs4963153 (SLC25A22)、rs9460 (ADPGK)、rs11191548 (NT5C2) 和 rs3008747（CCDC171等位基因特异性方式。结论 总之，我们的研究表明，一些已建立的 BMI 变体可能通过改变 miRNA 与 3'UTR 靶位点的结合来发挥作用。