Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome – Pilot study. (20th August 2022)

• Record Type: Journal Article
• Authors: Wander, Pandora L.; Enquobahrie, Daniel A.; Bammler, Theo K.; MacDonald, James W.; Srinouanprachanh, Sengkeo; Kaleru, Thanmai; Khakpour, Dori; Trikudanathan, Subbulaxmi
• Is Part Of: Molecular and cellular endocrinology. Volume 554(2022)
• Publication Date: 2022-08-20
• Subjects: PCOS -- Waist circumference -- Insulin resistance -- Biomarkers -- microRNAs; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2022.111723
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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 biomarkers 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 (β = −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 (β = −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. Highlights: microRNAs are non-coding RNAs that pair to messenger RNAs leading to repression or a decrease in stability. Plasma microRNA-1294 may be associated with obesity and insulin resistance in polycystic ovary syndrome. Larger studies among women with and without PCOS are needed to validate these findings.