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Article

Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study

1
Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, UK
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Institute of Molecular Biology and Genetics NAS, 03143 Kiev, Ukraine
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Institute of Paediatrics, Obstetrics and Gynaecology of the National Academy of Medical Sciences, 04050 Kiev, Ukraine
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Section of Statistical Multi-Omics, Department of Clinical & Experimental Medicine, School of Biosciences & Medicine, University of Surrey, Guildford GU2 7XH, UK
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Institute of Biochemistry and Genetics, Ufa Federal Research Centre Russian Academy of Sciences, 119192 Ufa, Russia
*
Authors to whom correspondence should be addressed.
Genes 2021, 12(1), 64; https://doi.org/10.3390/genes12010064
Received: 10 November 2020 / Revised: 22 December 2020 / Accepted: 23 December 2020 / Published: 5 January 2021
(This article belongs to the Special Issue Genetics and Genomics of Reproductive Medicine)
We assessed the predictive ability of a combined genetic variant panel for the risk of recurrent pregnancy loss (RPL) through a case-control study. Our study sample was from Ukraine and included 114 cases with idiopathic RPL and 106 controls without any pregnancy losses/complications and with at least one healthy child. We genotyped variants within 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased risk of RPL (odds ratio 1.56, 95% CI: 1.21, 2.04, p = 8.7 × 10−4). The receiver operator characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an improved ability of the GRS to classify women with and without RPL. Ιmplementation of the GRS approach can help define women at higher risk of complex multifactorial conditions such as RPL. Future well-powered genome-wide association studies will help in dissecting biological pathways previously unknown for RPL and further improve the identification of women with RPL susceptibility. View Full-Text
Keywords: recurrent pregnancy loss; genetic risk score recurrent pregnancy loss; genetic risk score
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MDPI and ACS Style

Loizidou, E.M.; Kucherenko, A.; Tatarskyy, P.; Chernushyn, S.; Livshyts, G.; Gulkovskyi, R.; Vorobiova, I.; Antipkin, Y.; Gorodna, O.; Kaakinen, M.A.; Prokopenko, I.; Livshits, L. Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study. Genes 2021, 12, 64. https://doi.org/10.3390/genes12010064

AMA Style

Loizidou EM, Kucherenko A, Tatarskyy P, Chernushyn S, Livshyts G, Gulkovskyi R, Vorobiova I, Antipkin Y, Gorodna O, Kaakinen MA, Prokopenko I, Livshits L. Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study. Genes. 2021; 12(1):64. https://doi.org/10.3390/genes12010064

Chicago/Turabian Style

Loizidou, Eleni M., Anastasia Kucherenko, Pavlo Tatarskyy, Sergey Chernushyn, Ganna Livshyts, Roman Gulkovskyi, Iryna Vorobiova, Yurii Antipkin, Oleksandra Gorodna, Marika A. Kaakinen, Inga Prokopenko, and Ludmila Livshits. 2021. "Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study" Genes 12, no. 1: 64. https://doi.org/10.3390/genes12010064

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