The role of maternal HLA-DR and HLA-G loci in determining the risk of sporadic congenital heart defects in the next generation

The paper considers the role of maternal HLA-DR (Human Leukocyte Antigens-DR) and HLA-G (Human Leukocyte Antigen-G) loci in determining the risk of the formation of sporadic congenital heart defects without chromosomal diseases in the next generation. The HLA-G molecule expressed on trophoblast performs a protective function by blocking killer receptors on natural killer cells (NK cells). At the same time, the maternal alleles of HLA-DRB1 restrict the immune response to allogeneic antigens of the paternal embryo, which may affect the severity of inflammation in the mother-embryo system and through this mechanism induce the formation of heart disease. Objective: to study the frequency distribution of the combinations of alleles and genotypes of HLA-G 3’UTR and HLA-DRB1 in women with children with sporadic congenital heart defects without chromosomal diseases. Children characteristics and research methods. There were formed 2 groups: Main Group (103 women with children with sporadic congenital heart defects without chromosomal diseases) and Control Group (103 women with conditionally healthy children). Genomic DNA was isolated by phenol-chloroform extraction. Typing of HLA-G 3’UTR 14-bp insertion/deletion was performed by amplification of polymorphic regions of genes by polymerase chain reaction with further electrophoretic detection in polyacrylamide gel 6.0. The frequency analysis of 14 alleles of the HLA-DRB1 gene was performed by real-time polymerase chain reaction. In the course of this work the authors identified predictor and protective combined genotypes. Conclusion. HLA-DRB1 and HLA-G 3’UTR 14-bp ins/del (rs 1704) make a significant contribution to determining the risk of the formation of sporadic congenital heart defects without chromosomal diseases in the next generation.