Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study

Background: Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive bio-markers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS. Methods: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR)-adjusted cutoff p < 0.1 to correct for multiple testing. We used miRDB's Gene Ontology (GO) tool to identify predicted pathways for top hits. Results: Mean age and BMI of participants were 27.9 years and 32.5 kg/m(2), respectively. Lower levels of miR-1294 were associated with higher waist circumference (beta =-0.10, FDR = 0.095). While no miRNAs were associated with HOMA-IR at our FDR cut off < 0.1, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at unadjusted p < 0.01, including members of the highly conserved miR-17/92 cluster and miR-1294 (beta =-0.10, p < 0.001). The GO analysis of miR-1294 identified 54 overrepresented pathways, including negative regulation of insulin receptor signaling (FDR = 0.019), and 6 underrepresented pathways. Conclusions: Plasma miR-1294 along with members of the miR-17/92 cluster and miRNAs involved in insulin signaling may be associated with central obesity and insulin resistance in PCOS. Larger studies among women with and without PCOS are needed to validate these findings.

Automated summary

This study found that circulating miRNAs, especially miR-1294, are associated with central obesity and insulin resistance in PCOS patients, suggesting their potential role in the pathogenesis of PCOS.