Abstract
The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. The main problems of active search for genetic predictors RM has become the phenomenon of «missing heritability». Complex diseases, including miscarriage are believed to have a polygenic basis and gene-gene interactions can play a significant role in the etiology of the disease. Gene-gene interactions can be a source of RM «missing heritability». This study was conducted to investigate the association of gene-gene interaction of angiogenesis and endothelial dysfunction genes polymorphisms and RM. It is shown that alleles of the 677T gene of the MTHFR gene, 894T of the NOS3 gene, genotypes of the 936CT and 936TT of the VEGF gene are associated with a predisposition to this pathology in the Russian ethnic group. The significant role of additive and epistatic effects in the intergenic interactions of the polymorphic variants of the SERPINE-1, ACE, NOS3, MTHFR , and VEGF genes to recurrent miscarriage susceptibility has been demonstrated. It has been shown that the analysis of a combination of genotypes of several allelic variants is more informative in assessing the risk of developing miscarriage than an association analysis at the level of single polymorphic markers.
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