Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States; Division of General Internal Medicine, University of Washington, Seattle, WA, United States.
Department of Epidemiology, University of Washington, Seattle, WA, United States.
Mol Cell Endocrinol. 2022 Aug 20;554:111723. doi: 10.1016/j.mce.2022.111723. Epub 2022 Jul 14.
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.
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.
Mean age and BMI of participants were 27.9 years and 32.5 kg/m, 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.
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.
胰岛素抵抗（IR）和中心性肥胖在多囊卵巢综合征（PCOS）中很常见，但 PCOS 中 IR 的发病机制尚不清楚。循环 microRNAs（miRNAs）是表观遗传调控的非侵入性生物标志物，可能有助于 PCOS 中 IR 和中心性肥胖的发病机制。
我们进行了一项初步研究，使用高通量 miRNA 测序检查了 PCOS 患者（n=11）循环 miRNA 与 IR 和中心性肥胖的关系。我们拟合了广义线性模型，以检验腰围和 HOMA-IR 与血浆 miRNA 的关系。我们使用 FDR 校正的 p<0.1 来校正多重检验。我们使用 miRDB 的基因本体论（GO）工具来识别 top hits 的预测途径。
参与者的平均年龄和 BMI 分别为 27.9 岁和 32.5kg/m2。miR-1294 水平较低与腰围较大有关（β=-0.10，FDR=0.095）。虽然没有 miRNA 在我们的 FDR 截止值<0.1 时与 HOMA-IR 相关，但在未调整的 p<0.01 时，有 11 个 miRNA 与腰围相关，有 14 个 miRNA 与 HOMA-IR 相关，包括高度保守的 miR-17/92 簇和 miR-1294 的成员（β=-0.10，p<0.001）。miR-1294 的 GO 分析确定了 54 个过表达途径，包括“胰岛素受体信号的负调控”（FDR=0.019）和 6 个低表达途径。
血浆 miR-1294 以及 miR-17/92 簇的成员和参与胰岛素信号的 miRNAs 可能与 PCOS 中的中心性肥胖和胰岛素抵抗有关。需要在有和没有 PCOS 的女性中进行更大规模的研究来验证这些发现。
