Background: Merely 2% of pregnant mothers experience two consecutive miscarriages, and as many as 50% of patients suffering from Recurrent Pregnancy Loss (RPL) lack a definitive cause for their condition. The CTLA-4 gene is located in band q33 on chromosome 2 of the human genome, is approximately 6.2 kilobases long, and is composed of 3 introns and 4 exons. In decidual and peripheral dendritic cells, it is expressed on human placental regulatory T (Treg) cells. Human miscarriages were associated with a downregulation of Treg cells and CTLA-4 expression in decidual and peripheral lymphocytes. The purpose of our analysis was to determine whether the CTLA-4 +49A/G (rs231775) & (rs3087243) gene polymorphism and unexplained RPL were related. Subjects and Methods: This case-control study included women with RPL were contrasted with healthy females at the age of motherhood. The study was conducted at the National Research Centre (Clinical Genetics Department -Human Cytogenetic Department - Molecular Genetics and Enzymology Department) in collaboration with Benha Faculty of Medicine (Clinical and Chemical Pathology Department).
Results: Considering AG is the reference haplotype, no significant association was found between CTLA-4 rs231775-rs3087243 haplotypes with number of abortions. rs231775 AG+GG was considered a protective predictor, while rs3087243 GA+AA was considered a risky predictor of susceptibility to spontaneous recurrent abortion in uni- and multivariable analyses. Conclusion: Our study revealed that a significant correlation was discovered between the CTLA-4 gene rs231775 AG, GG genotypes, G allele, rs231775- rs3087243 GG haplotype with protective effect against RPL. Whereas, a significant correlation was discovered between the CTLA-4 gene rs3087243 GA, AA genotypes, A allele AA haplotype and RPL risk.