Risk of recurrent pregnancy loss in the Ukrainian population using a combined effect of genetic variants

Abstract

19Recurrent pregnancy loss (RPL) affects nearly 5% of the women of reproductive age. Its heterogeneous 20 and multifactorial nature complicate both diagnosis and treatment, as well as identification of the genetic 21 contribution to RPL. Evidence about the aetiology of RPL is controversial; however, several biological 22 mechanisms have been proposed. Given the current knowledge about the genetic susceptibility to 23 idiopathic RPL, we aimed to evaluate the predictive ability of a combined variant panel to the risk of 24 RPL in the Ukrainian sample of 114 cases and 106 healthy controls. We genotyped variants within the 25 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood 26 coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental 27 function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We 28 showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased 29 risk of RPL (odds ratio 1.56, 95% CI: 1.21,2.04, P=8.7x10 -4 ). The receiver operator characteristic 30 (ROC) analysis resulted in the area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an 31 improved ability of the GRS to classify women with and without RPL. In summary, implementation of 32 the GRS approach can help defining women at higher risk to complex multifactorial conditions such as 33 RPL. Future well-powered genome-wide association studies will help in the dissection of biological 34 pathways not hypothesised previously for RPL and further improve the prediction and identification of 35 those at risk for RPL. 36 37 38

Unraveling the Balance between Genes, Microbes, Lifestyle and the Environment to Improve Healthy Reproduction

“…In this context, Barban et al [ 56 ], analyzing about 700,000 individuals, identified 12 loci associated with reproductive behavior highlighting also candidate genes and potentially causal variants [ 56 ]. Recently, Loizidou et al [ 57 ] assessed in a Ukainian cohort an association between 12 genetic loci and recurrent pregnancy loss [ 57 ]. In addition to the possibility to discover novel candidate genes and mutations, these GWASs on common genetic risk factors provide novel clues to interpret the underlying relationships and causality involved in the regulation of reproduction and fertility.…”