D2.428 - Contribution of Allelic Gene Variants of the Indoleamine-2,3-Dioxygenase and Dectin-1 to the Risk of Invasive Aspergillosis in Oncohematological Patients

Genetic determinants that define the functional activity of genes and the proteins they encode may be risk factors influencing the occurrence of Aspergillus spp. infections in oncohematological patients. The objective was to assess the association between polymorphisms in the pentraxin (PTX3), indoleamine-2,3-dioxygenase (IDO), and Dectin-1 genes and the risk of invasive aspergillosis (IA) in oncohematology patients after polychemotherapy.

The main group consisted of patients with verified IA (n=148), median age – 59.5 years, men – 51%. Among them, 118 patients were diagnosed with "probable" and 30 patients with "possible" IA according to the EORTC/MSRS criteria. The control group included 150 patients with signs of lung damage and excluded IA with median age 58 years, men – 58%. DNA samples for the molecular genetic study were obtained from the peripheral venous blood. Polymorphic variants of the PTX3, IDO1 and Dectin-1 genes were determined by real-time PCR using allele-specific fluorogenic probes TaqMan (Thermo Scintific, USA). Statistical analysis was performed using STATISTICA, version 13.

The underlying oncohematological diseases in patients of the study and control groups were lymphomas in most cases (36.5% and 57.3%, respectively). Patients with acute leukemia prevailed in the group of patients with IA and constituted 43.9% (in the control group - 18.6%). No relationship was found between the increased risk of developing IA and the presence of polymorphic variants rs2305619, rs1840680 and rs3816527 of the PTX3 gene.  In the cohort of oncohematological patients with IA the homozygous wild-type genotype CC of the IDO1 gene polymorphic variant rs7820268 was statistically significantly predominant (p<0.001). The odds ratio of the risk of developing IA was 6.035 (95% CI: 2.018-18.048, p<0.001). It was found that patients carrying the GG genotype for the polymorphic variants rs7309123 in the Dectin-1 gene (n = 48) had a significantly higher risk of developing IA (OR = 2.520; 95% CI: 1.445-4.394; p = 0.002).

The homozygous variants of CC rs7820268 of the IDO1 gene and GG rs7309123 of the Dectin-1 gene were identified as genetic risk factors for the development of IA in oncohematological patients.