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Genetic Risk Factors for Inhibitor Development in Hemophilia A

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Abstract

The review is devoted to the description of possible mechanisms of inhibitor development in hemophilia A. Most of the focus is on the genetic factors, but attention is also paid to factors of different nature, as well as their combinations that can provoke the synthesis of inhibitory antibodies. Among the genetic determinants, special attention is paid to the type of factor VIII gene mutations, as well as functional SNPs in the protein-coding genes that regulate the immune system, which were studied by different research groups using both classical and the most modern molecular genetic methods. The type of F8 gene mutations remains the most unbiassed genetic risk factor for the inhibitor development; moreover, studies aimed at the analysis of combinations of the F8 missense mutations, causing the synthesis of antibodies, with HLA class II alleles are of particular interest. For other genetic markers, further studies are required to verify their putative role in the development of the inhibitory form of hemophilia A. Among the nongenetic factors, the inhibitor development largely depends on the type of FVIII product and the intensity of therapy. However, despite numerous studies, hemophilia inhibitors remain the most difficult treatment option of this disease. In solving this problem, the construction of algorithms for predicting the risk of inhibitor development using the integration analysis that takes into account multiple factors of both genetic and other nature and their interaction can help.

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  1. National Research Center for Hematology, 125167, Moscow, Russia

    O. S. Pshenichnikova & V. L. Surin

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Pshenichnikova, O.S., Surin, V.L. Genetic Risk Factors for Inhibitor Development in Hemophilia A. Russ J Genet 57, 867–877 (2021). https://doi.org/10.1134/S1022795421080111

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