S848 ALLELIC POLYMORPHISM OF PLATELET GLYCOPROTEIN GENES GPIA AND GPIIB AS A POSSIBLE PREDICTIVE MARKER OF RESPONSE TO THERAPY IN PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA

Background: Primary immune thrombocytopenia (ITP) is characterized by variability of both clinical course (in particular, severity of hemorrhagic syndrome) and response to distinct therapy options. To date, the choice of therapeutic approach to ITP treatment is empirical and often based on the experience of clinician. It is assumed, that allelic polymorphism (AP) of some genes coding for glycoproteins (GP), involved in regulation of immune response or/and platelets’ functional activity, can be associated with different response to ITP treatment, which provides an opportunity for individual approach to therapy. Aims: To investigate association between the effectiveness of certain methods of ITP treatment and the features of AP of GPIa and GPIIb genes in the groups of patients with different response to corticosteroids (CS) in the first line, thrombopoietin receptor agonists (aTPOr) and splenectomy (SE) in the second line of therapy. Methods: A total of 81 patients with primary ITP were involved in the study, all of them received 1‐st line treatment with CS, then 37 (46%) patients received aTPOr and 22 (27%) underwent SE in the 2‐nd line. In respect with the effectiveness of each therapy option, we divided the patients to 3 following groups: “achievement of response”, “no response” and “durable response”. In all patients, we analyzed DNA polymorphism of GPIa (A1648G) and GPIIb (T2622G) genes by PCR‐RFLP. The differences in genotype frequencies between the patient groups with distinct response to treatment were assessed by Fisher's exact method. Odds ratios (OR), their 95% confidence intervals (CI) and p‐values were calculated by using the Graph Pad Prism 5.0 software. Results: The frequency of heterozygous GPIIb 2622TG genotype in patients with durable response to CS was more than 2‐fold increased when compared to those with response (72.2% vs. 30.9% respectively; OR = 5.8, 95% CI: 1.7–19.7, p = 0.005). Homozygotes for the GPIa 1648A allele were much more prevalent among the patients who responded to aTPOr (87.5% vs. 20.0% in the no response group; OR = 28.0, 95% CI: 2.5–317.9, p = 0.005). Moreover, all patients with durable response to SE possessed GPIa 1648AA genotype, whereas in the group of patients with no response the proportion of such persons was only 44% (OR = 33.0, 95% CI: 1.5–722.5, p = 0.005). Summary/Conclusion: Genotype GPIIb 2622TG is associated with durable response to CS in the 1‐st line treatment of ITP patients. The presence of GPIa 1648AA variant could predict the effectiveness of aTPOr or SE in the 2‐nd line of therapy.