Identification of genes associated with recurrent pregnancy loss among Kazakhstani population

Grant Funding 2022-2024
Ministry of Education and Science of the Republic of Kazakhstan

Using exome sequencing approaches, we aim to evaluate the presence of novel genetic variants to identify unsuspected genomic regions, which may predispose to the development of subsequent RPL.
2.3. Project objectives
Objective: To perform whole exome sequencing of women with idiopathic RPL.
Specific aims:
1. To identify novel genetic variants associated with the development of idiopathic RPL, specifically in relation to their ethnic/racial background. We plan to identify variants that are associated with no live births (nuli-para) as well as those seen in RPL cases with at least one live birth.
2. To validate the identified variants, by investigating their presence in a large cohort of women with RPL and control women.
3. To investigate the association of the confirmed variants with RPL-associated features and risk factors, namely obesity, autoimmunity, and psychological changes.

Recurrent pregnancy loss (RPL) is a multi-factorial disorder, and its exact cause and pathology remains poorly understood. Many lines of evidence implicate genetic susceptibility in determining the risk of RPL. Previous reports show the association of a number of GWAS-identified at-risk genetic variants, along with HLA class II DP/DQ/DR polymorphisms, with altered risk of RPL. A limitation of this approach was the failure to identify additional, likely key genetic factors, linked with altered risk of RPL, given the experimental approach used (replication studies).

It is anticipated that results obtained from these studies will help in shaping future strategies to search for additional susceptibility genes in RPL, which in turn will have a significant impact in its diagnosis, management, and long-term follow up. In view of the heterogeneity of RPL, and its mode of presentation and prevalence among different races and communities, results obtained will be of direct significance to the population of Kazakhstan, where prevalence rates vary among its oblasts, and remains poorly managed and followed-up. Our research team has investigated the association of FOXP3 polymorphism, which controls the continued development of regulatory T-cells, with RPL in Kazakhstani women. The study confirmed the negative association of rs22944021 and positive association of rs2232365 FOXP3 variants with idiopathic RPL