Relationship to Perilipin 1 (PLIN1) Gene Regulation by Circulating microRNAs.

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Childhood obesity is a growing public health burden in many countries. The lipid perilipin 1 (PLIN1) gene is involved in regulation of lipolysis, and thus represents a viable candidate mechanism for obesity genetics research in children. In addition, the regulation of candidate gene expression by circulating microRNAs (miRNAs) offers a new research venue for diagnostic innovation. We report new findings on associations among circulating miRNAs, regulation of the PLIN1 gene, and susceptibility to childhood obesity. In a sample of 135 unrelated subjects, 35 children with obesity (between ages 3 and 13) and 100 healthy controls (between ages 4 and 16), we examined the expression levels of four candidate miRNAs (hsa-miR-4777-3p, hsa-miR-642b-3p, hsa-miR-3671-1, and hsa-miR-551b-2) targeting the PLIN1 as measured by real-time polymerase chain reaction in whole blood samples. We found that the full genetic model, including the four candidate miRNAs and the PLIN1 gene, explained a statistically significant 12.7% of the variance in childhood obesity risk (p = 0.0034). The four miRNAs together explained 10.1% of the risk (p = 0.008). The percentage of variation in childhood obesity risk explained by hsa-miR-642b-3p and age was 19%. In accordance with biological polarity of the observed association, for example, hsa-miR-642b-3p was upregulated, while the PLIN1 expression decreased in obese participants compared to healthy controls. To the best of our knowledge, this is the first clinical association study of these candidate miRNAs targeting the PLIN1 in childhood obesity. These data offer new molecular leads for future clinical biomarker and diagnostic discovery for childhood obesity.

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