ᐊ P5-31
Open Readings 2021 • P5-33
P5-34 ᐅ

ANALYSIS OF CIRCULATING MIRNA LEVELS IN BLOOD OF WOMEN DIAGNOSED WITH GESTATIONAL DIABETES

Gabrielė Dzimitravičiūtė1, Kristina Daniūnaitė1

1 Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania

[email protected]

Gestational diabetes mellitus (GD) is a chronic hyperglycemia diagnosed during the 2nd trimester of pregnancy [1]. Despite the tendency to disappear after delivery, the prevalence of this disease is constantly growing in Lithuania and worldwide and correlates with the type 2 diabetes mellitus (T2D) as GD causes higher risk of T2D for the mother and her child [2, 3]. Therefore, it is important to elucidate molecular biomarkers for the risk evaluation of both GD and T2D development.

As epigenetic alterations show great perspectives as liquid-biopsy biomarkers [4], the aim of this study was to analyze 6 selected microRNAs – miR-16-5p, miR-27a-3p, miR-152-3p, miR-155-5p, miR-222-3p, and miR-518d-5p in whole-blood samples of women diagnosed with GD and to associate them with clinical GD indicators.

In total, 56 women (49 diagnosed with GD and 7 healthy pregnant women) were included in the study and 108 samples were tested. Blood samples were taken at 24–28 weeks of gestation (n = 39), at 6–12 weeks after delivery (n = 12), and also from the umbilical artery (n = 26) and vein (n = 26). The selected miRNAs were quantified by means of quantitative PCR using TaqMan-based assays after reverse transcription (RT) of all miRNAs.

Higher amounts of miR-16-5p, miR-152-3p, miR-155-5p and miR-222-3p were detected in the blood of GD women after delivery compared to the gestational period (all p < 0.05). Also, higher levels of miR-16-5p, miR-27a-3p and miR-152-3p were detected in the blood of GD women after delivery as compared to healthy not pregnant women (all p < 0.05; Fig. 1). The miRNA levels did not differ between the GD and non-GD women in blood during gestational period (all p > 0.05). MiR-518d-5p was detected only in blood from the umbilical artery. The amount of miR-16-5p in GD women during gestational period was associated with body mass index before pregnancy, while miR-27a-3p and miR-155-5p correlated with plasma glucose levels (all p > 0.05). Furthermore, the blood level of miR-155-5p after delivery was associated with women's age (p = 0.017) and similar tendencies were observed regarding miR-16-5p and miR-222-3p in blood from the umbilical vein.

Figure 1
Fig. 1. Comparison of miRNA blood levels among GD women during gestational period, GD women after delivery and healthy not pregnant women. A – miR-16-5p, B – miR-27a-3p, C – miR-152-3p, D – miR-155-5p, E – miR-222-3p. The middle line in the box - median, + mean, top and bottom lines of the box – 75 % and 25 % quartiles (respectively), whiskers – maximum and minimum values, dots - outliers.

This study showed various associations between the levels of analyzed miRNAs in the blood of GD women and their clinical indicators, indicating their potential for GD and T2D diagnostics and / or prognosis. However, comprehensive studies in larger cohorts are needed to validate these miRNAs as potential GD biomarkers.

[1] R. Ding et al. Integrated transcriptome sequencing analysis reveals role of miR-138-5p/ TBL1X in placenta from gestational diabetes mellitus. Cellular Physiology and Biochemistry. 2018;51(2):630.

[2] J. Répšaitė et al. Connection of gestational diabetes and metabolic syndrome among women diagnosed with gestational diabetes more than 15 years ago. Kaunas: Lithuanian University of health sciences. 2017.

[3] S. Dias et al. Molecular Biomarkers for Gestational Diabetes Mellitus. International Journal of Molecular Sciences. 2018;19(10):2926.

[4] C. V. Collares et al. Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients. BMC Research Notes. 2013;6:491.