Plasma TLR2 and IGF2/H19 imprinting control region gene methylation in fetal growth restriction


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Abstract

Aim. To investigate the level of TLR2 and IGF2/H19 imprinting control region methylation in peripheral blood plasma in fetal growth restriction (FGR). Material and methods. The study included 118pregnant women divided into those who had (group 1, n=58) and who had not had (group 2, n=60) a confirmed diagnosis of IGR. In group 1, 24 and 34 women had early and late FGR, respectively. Testing for methylation level of 22genes was conducted using Methylation-Sensitive High-Resolution Melting (MS-HRM). Results. TLR2 methylation level was statistically significantly reduced to 0.01 (0.0; 0.45) in early FGR. At the relative level of TLR2 methylation threshold of 0.012, the sensitivity and the specificity were 88.1% and 60.2% (AUC=0.72, 95% CI 0.56-0.88). No statistically significant differences were found in late FGR compared with a healthy pregnancy. The level of plasma IGF2/H19 imprinting control region methylation was reduced in early FGR, reaching 0.22 (0.18; 0.32); in the comparison group it was 0.49 (0.44; 0.65), (p=0.03). At the threshold of 0.2 of the relative IGF2/H19 imprinting control region methylation, the sensitivity and specif icity were 80.4% and 80.1%, respectively. The relative level of ICR IGF2/H19 methylation in late FGR did not differ significantly from that in a healthy pregnancy. Conclusion. The study f indings conf irm that TLR2 and IGF2/H19 imprinting control region genes methylation have a role in FGR development and can be used as non-invasivepredictors. These results suggest that antenatal epigenetic changes continue in the neonatal period and are essential for fetal programming implementation.

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About the authors

N. E Kan

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russian Federation

Email: kan-med@mail.ru
Dr. Med. Sci., Professor, Deputy Director for Research 117997, Russia, Moscow, Ac. Oparina str., 4

V. L Tyutyunnik

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russian Federation; Perinatal Center, European Medical Center

Dr. Med. Sci., Professor, Leading Researcher at the Department of Research Administration, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russian Federation; Head Physician of the Perinatal Center, European Medical Center. 5099. 117997, Russia, Moscow, Ac. Oparina str., 4; 125040, Russia, Moscow, Pravda str., 15/1

Z. V Khachatryan

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russian Federation

Email: z.v.khachatryan@gmail.com
Ph.D. Student 117997, Russia, Moscow, Ac. Oparina str., 4

A. A Sadekova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russian Federation

Email: asadekova@oparina4.ru
Ph.D., Senior Researcher at the Cytology Laboratory 117997, Russia, Moscow, Ac. Oparina str., 4

A. M Krasnyi

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russian Federation

Email: alexred@list.ru
Ph.D. (bio.sci.), Head of the Cytology Laboratory 117997, Russia, Moscow, Ac. Oparina str., 4

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