Endogenous controls and microRNA profile in female patients with obstructive sleep apnea

Abstract

Recent studies have evaluated the potential of circulating microRNAs (miRNAs) as valuable biomarkers for characterizing obstructive sleep apnea (OSA) in males. The potential use of miRNAs as clinical indicators in females is unknown. The objective is to identify a set of miRNAs to be used as endogenous controls (ECs) in female patients with OSA. Then, to analyze differences in the miRNA expression profile between patients with and without OSA. This observational, longitudinal study included 85 females with suspected OSA who underwent a polysomnography. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The study population was stratified into 50 OSA patients and 38 non-OSA patients. Exploratory expression profiling of 188 miRNAs consistent and reliable in plasma was performed in a discovery cohort of 21 patients by TaqMan-Low-Density-Array (TLDA). The best ECs were identified by mean centre + standard deviation normalization and concordance correlation restricted normalization. Differentially expressed candidate miRNAs were selected for RT-qPCR validation in a validation cohort of 64 patients. Three circulating miRNAs (miR-30a-5p, miR-93-3p and miR-532-5p) were identified as most stable for use as ECs. Twenty-seven miRNA candidates were identified as potential biomarkers for OSA screening (p value < 0.025) in the TLDA cohort. However, validation cohort showed no differences in the circulating miRNA profile in female patients with and without OSA. We identified a set of ECs in females with OSA that may contribute to result homogeneity in determining circulating miRNAs. Exploratory analysis did not identify a significantly miRNA profile between female patients with and without OSA.

The impact of obesity, age, and gender on plasmatic levels of selected glycoprotein biomarkers and miRNA-499 in OSA patients

“…These findings are consistent with those of Kelch et al (2017) and Meder et al (2014). Zapater et al (2022) addressed gender differences for miRNAs in the OSA-targeted population, but their work investigated mi-croRNA molecules different from ours. It should also be noted that there is still a lack of research on this topic.…”

“…Recent scientific literature has papers dealing with the potential of microRNAs in the field of OSA. Zapater et al (2022) published a paper highlighting the high potential of micro RNAs in this regard. Sánchez-de-la-Torre et al (2015, co-authors of other publications agree that it is now possible to identify specific microRNAs associated with OSA and comorbidities.…”

“…Several studies have investigated the relationship between OSA and biomarkers of inflammation (Imani et al, 2021;Sahlman et al, 2010), cardiovascular disease (Neumann et al, 2019), metabolism (Denver et al, 2011;Punjabi et al, 2002), oxidative stress (Katsoulis et al, 2011;Lavie, 2009), and adhesion molecules (Lv et al, 2021;Pak et al, 2015). While miRNAs, a group of markers that are easily accessible from peripheral blood sampling, relatively small in size (21-23 nucleotides), and exhibit good stability (Zapater et al, 2022), have shown promise in OSA research, research on their association with the disease is still in its early stages.…”

Micro-RNA in obstructive sleep apnoea: biomarker of cardiovascular outcome?

“…Subsequently, due to the sex-disparity in miRNA expression patterns [37], the same methodology was performed in females. A set of three miRNAs (miR-30a-5p, miR-93-3p and miR-532-5p) was identified as the most stable to be used as endogenous controls in the determination of circulating miRNAs in OSA [38]. Subsequently, Santamaria-Martos et al [39] identified a profile of six miRNAs that contributes significantly to the diagnosis of the disease.…”