Diagnostic value of copy number identification of the SERPING1 gene in patients with different types of hereditary angioedema associated with C1-esterase inhibitor deficiency

Guryanova I.E., Polyakova E.A., Liubushkin A.V., Korosteleva L.B., Kazak V.I., Zharankova Yu.S., Lutskovich D.V., Belevtsev M.V.

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk

Introduction. Hereditary angioedema (HAE) is a rare, genetically mediated, difficult to diagnose, and life-threatening disease, with an expected incidence of about 1 in 10 000 to 1 in 50 000 people with no racial or gender differences. The significance of the issue is proven by the difficulties in diagnosis and treatment of patients with HAE, as well as the profound impact of the disease on patients' lives.

Aim. To assess the diagnostic value of copy number identification of the SERPING1 gene in patients with different types of hereditary angioedema associated with C1-esterase inhibitor deficiency.

Materials and methods. The study included samples of сDNA from the control group (n=50) and HAE patients with allelic variants in the SERPING1 gene (n=17). The number of copies of the SERPING1 gene was determined by real-time PCR. Own plasmid standards obtained by cloning gene sequences of interest into the pTZ57_R Vector were used as calibrators. The number of copies of the SERPING1 gene per 1 million cells was calculated by the formula: [106 × average number of copies of the SERPING1 gene / average number of copies of the CD64 gene].

Results. In the group of patients with HAE type I, the diagnostic sensitivity of determining the number of copies of the SERPING1 gene was 83.3%, the diagnostic specificity was 94%, the diagnostic efficiency was 90.4%, the predictive validity of a positive result was 100%, the predictive validity of a negative result was 94.5%. In the group of patients with HAE type II, the diagnostic sensitivity was 40%, the diagnostic specificity was 78%, the diagnostic efficiency was 90%. The obtained data on the determination of copy number identification of the SERPING1 gene in patients with different types of hereditary angioedema associated with C1-esterase inhibitor deficiency in comparison to the measurement of antigenic C1-esterase inhibitor in the blood serum demonstrate feasible results for use in laboratory practice.