Sosnina K. Immunogenetic prerequisites of early reproductive losses in human

The thesis is devoted to the study of immunogenetic prerequisites of early reproductive losses in human. The initial concept of work was based on the assumption that a mutation of genes of major histocompatibility complex on the one hand and changes in genes whose products interact with this complex (HLA-system),on the other hand, can be one of the causes of early reproductive losses. It has been established that allele HLA-DRB1 *0301 is likely to be associated with recurrent pregnancy loss, and its presence increases the risk of RPL for women by 2.4 times. In women with primary infertility DQB1 *0201 allele plays a key role, and its presence increases the risk of infertility for women by two times. It has been determined that homology for genes of two (DRB1+DQA1) loci of HLA-class II increases the risk of RPL in a couple by 50 percent and higher to 2.68 times. In the case of homology for genes of three (DRB1+DQA1+DQB1) loci this risk increases by 12.8 times. A similar trend has been observed in couples with primary infertility. The distribution and genotype frequencies of HLA-G 14 bp insertion/deletion polymorphism in biological material of spontaneously aborted embryos have been studied for the first time. Calculation of odds ratio (OR) has showed that the genotype insertion/insertion 14 bp of HLA-G in embryos or in women increases the risk of recurrent pregnancy loss by more than twice. The analysis of SNP at positions -1082G/A,- 592C/A, -819C/T of IL-10 and SNP +874A/T of IFN-? has shown that the risk of recurrent pregnancy losses increases by three times at 1082GG, 592CC and 819CC - genotypes of IL-10 gene and by 2 times at 874AA genotype of IFN-? gene. As a result, for the first time there has been offered the scientific grounds and reasonability of studying of immunogenetic markers of prerequisites of early pregnancy losses and the scheme of complex immunogenetic examinations for the couples with reproductive failure in anamnesis has been offered. This scheme is described as: the homology of couple by 50 percent or higher by genes of HLA-class II system, the presence of DRB1*0301 allele in a woman's genome, homozygous HLA-G 14 bp insertion/insertion genotype, 1082GG, 592CC, 819CC genotypes of interleukin-10 gene and 874AA genotype of interferon-? gene.