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SNP dependent modulation of circulating miRNAs from the miR25/93/106 cluster in patients undergoing weight loss.
Gene ( IF 3.5 ) Pub Date : 2020-05-18 , DOI: 10.1016/j.gene.2020.144787
Stephanie Müller 1 , Stefan Wallner 2 , Gerd Schmitz 2 , Thomas Loew 3 , Thomas Stempfl 4 , Christoph Möhle 4 , Christina Strack 5 , Sabine Sag 5 , Andrea Baessler 5 , Marcus Fischer 5
Affiliation  

BACKGROUND Diet induced weight loss represents an intervention for obesity to prevent associated diseases. However there is considerable inter-individual variation. Single nucleotide polymorphisms (SNPs) and plasma miRNA might be contributing factors. We therefore hypothesized that changes in the miRNA pattern during weight loss depend on the SNP genotype. METHODS Plasma miRNA profiles from 12 patients were determined before and after a three month weight loss intervention by Illumina sequencing. 46 further patients were analyzed by qPCR. SNP genotypes were determined on the Sequenom iPLEX platform. RESULTS Samples before and after weight loss were analyzed by miRNA-seq and delta miRNA levels ranked according to p-value. Levels of miRNAs 25, 93 and 106 that are expressed from a common genomic cluster were reduced after weight loss. Those results were substantiated in a qPCR analysis of 46 additional patients. This is in accordance with mouse data showing a functional involvement of this cluster in obesity. Correlation of the changes in miRNA abundance with SNP genotypes revealed a statistical association of all three miRNAs with known obesity susceptibility SNPs. CONCLUSION Diet induced weight loss leads to SNP dependent modulation of miRNAs from the miR 25/93/106 gene cluster in humans.

中文翻译:

减肥患者中来自miR25 / 93/106簇的循环miRNA的SNP依赖性调节。

背景技术饮食引起的体重减轻代表对肥胖症的预防以预防相关疾病。但是,个体之间存在相当大的差异。单核苷酸多态性(SNP)和血浆miRNA可能是促成因素。因此,我们假设减肥过程中miRNA模式的变化取决于SNP基因型。方法通过Illumina测序在三个月的体重减轻干预前后,确定了12例患者的血浆miRNA谱。通过qPCR分析了另外46名患者。在Sequenom iPLEX平台上确定了SNP基因型。结果通过miRNA-seq和delta miRNA水平根据p值对体重减轻前后的样品进行了分析。体重减轻后,从常见基因组簇表达的miRNA 25、93和106的水平降低。这些结果在另外46位患者的qPCR分析中得到了证实。这与显示该簇功能性参与肥胖的小鼠数据一致。miRNA丰度变化与SNP基因型的相关性揭示了所有三种miRNA与已知肥胖易感性SNP的统计关联。结论饮食引起的体重减轻导致人类中miR 25/93/106基因簇中miRNA的SNP依赖性调节。
更新日期:2020-05-18
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