Application of bioinformatical analysis to identify candidate genes associated with hereditary angioedema.

Primary immunodeficiencies (PID) are a heterogeneous group of hereditary diseases that lead to impaired immune defense. Often, the diagnosis cannot be made without identifying mutations that lead to the development of the disease. For many PIDs, there is no clear understanding of the etiology, pathogenesis, and genes involved. There is an obvious need to identify candidate genes potentially capable of leading to the development of PIDs.Hereditary angioedema (HAE) is a rare genetically determined disease, accompanied by recurrent edema of soft tissues and submucosal membranes, posing a threat to the life of patients. Diagnosis is based on the clinical presentation, family history, laboratory values ​​of C1-esterase inhibitor, complement component 4, complement component 1q, antibodies to C1 and genetic testing for a number of mutations in the genes SERPING1, F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6. However, pathogenesis may involve other genes in which the negative effect of mutations has not yet been studied. HAE is a non-monogenic disease that may involve an extensive network of genes. It seems important to determine the groups of the most probable candidate genes presumably involved in the development of pathology.Aim. To identify, using bioinformatics analysis, candidate genes for the development/pathogenesis of HAE and to reveal their biological context.Materials and methods. The analysis was based on a group of genes, mutations in which are significantly associated with HAE: SERPING1, F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6. To analised genetic and protein–protein networks and identify the biological context of the selected candidate genes, a number of web resources were used: HumanNetv3, GeneMania, FUMA GWAS in the GENE2FUNC mode.Results. One hundred potential candidate genes in which mutations can be associated with HAE have been identified. The biological context of the identified genes was determined. The data of the biological context, genetic and protein-protein interactions made it possible to exclude a number of genes from the list of the most likely participants in pathogenesis and divide the remaining ones into groups with a greater or lesser potential for involvement. The group of the most likely HAO candidate genes includes PLAT, HRG, SERPINA1, SERPINF2, MASP2, GRB14, C1QBP, DOK2, KLKB1, F11, TEK, KLK10, KRT1, APOH, CPB2, F2.Conclusion. The results obtained can provide significant assistance in the study of the HAE molecular mechanism, as well as in the diagnosis and prognosis of the disease course. The identified candidate genes have the potential to serve as diagnostic biomarkers for patients with unexplained angioedema.The use of bioinformatic methods makes it possible to determine the list of candidate genes that are presumably involved in the disease pathogenesis or aggravate its course, and to obtain up-to-date information about the biological context of the identified genes. Understanding the genetic underpinnings and pathophysiology of PID may help define new diagnostic and therapeutic targets

Prevalence of occult hepatitis B infection among blood donors in Saint Petersburg

The aim of this study was to assess the prevalence of occult hepatitis B infection among blood donors in St. Petersburg, as well as to characterize the identified virus isolates. The study material was represented by 2800 blood plasma samples collected in 2019 from blood donors living in St. Petersburg. The ELISA study for HBV marker rate consisted of HBsAg, anti-HBs IgG, anti-HBcore IgG. HBV DNA was analyzed by nested PCR with real-time hybridization-fluorescence detection on three targets allowing to determine virus DNA at low viral load, including HBsAg-negative chronic hepatitis B. Hepatitis B serological markers were detected in 69.43% of those surveyed, HBsAg was found in 0.43% of individuals, and all of which donated blood first time. A significant excess of the anti-HBcore IgG antibodies occurrence among primary donors (15.1%) compared with repeated/regular donors (7.48%) was shown. The prevalence of virus DNA in the group was 3.14%, including 2.71% of cases in HBsAg-negative CHB. Based on phylogenetic analysis of 88 isolates, HBV subgenotypes were determined in the following order: D1 and D2, 40.91% each, D3 and A2, 9.09% each. While determining the serological subtype in detected isolates, the serotype ayw3 (52.27%) vs ayw2 (46.59%) and adw2 (10.23%) prevailed. Drug resistance mutations, including compensatory ones, were detected in six examined patients (6.82%). In all genotype D isolates, multiple amino acid substitutions were identified in the RT, SHB, MHB, LHB, and Core regions; mutations in the preCore region were detected in 21.59% samples. In the MHR of the HBV genotype D genome, twenty-six positions were identified in which amino acid substitutions occurred, and all isolates showed modifications at positions 113, 114, 131, 134, 159, 161, 168, in 76 — at position 122, in 68 — at position 127, in 36 — at position 118, in 24 — at position 128. In HBV A2 isolates, mutations T113S, S143T, Y161F were identified. Nine isolates in the preCore region showed a polymorphism including a stop codon W28*W; in five isolates the W28S substitution was shown in the same position, and the W28*S variant was found in one more sample. The high incidence of HBsAg-negative CHB cases among blood donors, as well as the predominance of HBV isolates that simultaneously carry mutations resulting in diagnostic failure of HBsAg tests and prophylactic failure of immunoglobulin or vaccines and virus reactivation, mutations that contribute to disease progression obviously pose a threat to health and require to be further examined