학술논문

SNP dependent modulation of circulating miRNAs from the miR25/93/106 cluster in patients undergoing weight loss.
Document Type
Article
Source
Gene. Aug2020, Vol. 753, pN.PAG-N.PAG. 1p.
Subject
*WEIGHT loss
*MICRORNA
*REDUCING diets
*SINGLE nucleotide polymorphisms
*GENE clusters
*STATISTICAL association
*DISEASE complications
Language
ISSN
0378-1119
Abstract
• Sequencing reveals lower levels of circulating miRNAs 25/93/106 after weight-loss. • This could be reproduced by qPCR in independent samples. • All three miRNAs are encoded in a cluster on chromosome 7. • In mice these miRNAs are known modulators of adiposity and insulin resistance. • miRNA changes correlate with the genotype of obesity susceptibility SNPs. 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. 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. 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. Diet induced weight loss leads to SNP dependent modulation of miRNAs from the miR 25/93/106 gene cluster in humans. [ABSTRACT FROM AUTHOR]