Tularemia: Epidemiological, clinical, laboratory assessment and interferon gamma 874 t/a, nramp1 int4 gene polymorphisms study

ABSTRACT TULAREMIA: EPIDEMIOLOGICAL, CLINICAL, LABORATORY ASSESSMENT AND INTERFERON GAMMA 874 T/A, NRAMP1 INT4 GENE POLYMORPHISMS STUDY Tularemia is a zoonotic disease that can be seen as endemic in the northern hemisphere. Francisella tularensis, which is the causative agent of the disease, is a facultative intracellular pathogen. IFN- γ and NRAMP-1 play an important role for the control of the disease caused by intraocellular bacteria. In this study, we aimed to evaluate the epidemiological, clinical and laboratory characteristics of patients diagnosed with tularemia and to investigate the polymorphisms of NRAMP-1 Int4 and IFN-γ 874 T/A in these patients. The 53 patients diagnosed with tularemia between 2011 and 2017 were called. The 26 of these patients agreed to participate the control examination and genetic study. A control group with 100 healthy person was selected. For the statistical analysis, p<0.05 was considered as significant. A total of 33 (62.3%) patients were glandular, 19 (35.8%) were oropharyngeal, and 1 (1.9%) was ulceroglandular tularemia. Lymphadenopathy was not detected in 16 (61.5%) of 26 patients who participated in the study, whereas lymphadenopathy size was reduced in 10 (38.4%) patients according to the initial application records. In the patient group, IFN-γ genotypes were found as 48% for AA, 40% for AT, and 12% for TT. In the control group, the AA genotype was 30%, TT genotype was 24% and AT genotype was 46%. There was a statistically significant difference for the incidence rate of IFN-γ 874 A/T variant allel (AT/TT) between the patient and control group (p=0.038). NRAMP-1 int4 genotypes were found in the patient group such as 52% for G/G, 40% for G/C, and 8% for C/C. Allel distributions in the control group were 63% for G/G, 35% for G/C, 2% for C/C. The incidence rate of NRAMP-1 Int4 polymorphism was different between the patient and control group, but no statistically significant difference was found (p=0.248). This is the first study in which the relationship of INF-γ 874 T/A gene polymorphism with tularemia cases was investigated and significant results were found. There is a need for multi-center clinical studies to be done with more patients in this topic. Understanding genetic factors related to the susceptibility of the disease will help to identify pathogenesis, have new pharmacological targets, and develop effective vaccines. Keywords: Tularemia, polymorphism, INF-γ 874 T/A, NRAMP-1 Int4