Polimorfismo do fator de regulador de Interferon 1 (rs839) em pacientes com anemia falciforme: associação com biomarcadores clínicos e de inflamação

Abstract

Sickle cell anemia (SCA) is an autosomal recessive disease caused by a point mutation in the β-globin gene, resulting in hemoglobin S (HbS) in homozygosity. Under hypoxic conditions, HbS polymerizes, causing a conformational change in the red blood cells, termed sickle cells. The disease is characterized by chronic hemolytic anemia and recurrent vaso-occlusive crises, which trigger systemic inflammatory processes. Various modulators are associated with the inflammatory process in SCA, among which genetic polymorphisms may correspond to different phenotypes of the disease, making the identification of these variations essential for prognosis determination. Single nucleotide polymorphisms (SNP) of the interferon regulatory factor 1 (IRF1) have been associated to neoplasms and inflammatory diseases such as Chron’s disease, underscoring the need to investigate their impacts on SCA. This study aimed to evaluate the frequence of interferon regulatory factor 1 polymorphism (rs839) in patients with sickle cell anemia patients and its association with clinical and inflammatory biomarkers. Sixty-eight adult patients with SCA and 82 blood donors as a control group (CG) participated in the study. Epidemiological data (age and sex), anthropometric data (weight, height, and body mass index - BMI), clinical data (severe vaso-occlusion crisis, acute chess syndrome, stroke, avascular necrosis, leg ulcers, priapism, cholelithiasis, and cholecystitis), laboratory data, (blood count, reticulocyte count, and hemoglobin electrophoretic profile), and pharmacological data (use of hydroxyurea, dose, and duration) were obtained from medical records. The IRF1 polymorphism rs839 was determined by real-time PCR using TaqMan probes. A significance level of p < 0.05 was adopted. The majority of patients, 43 (63.2%), were female, and 38 (55,9%) had a BMI within the normal range. Regarding clinical presentation, 50 (73.5%) experienced non-severe vaso-occlusion crises in the last year, 57 (83.8%) had moderate anemia, and 48 (70.6%) were using hydroxyurea, with a dose of 21.8mg/kg/day, and 42 (61.8%) had been on medication for more than 5 years. There were statistical differences between hemoglobin (Hb), mean corpuscular volume (MCV), leukocytes, lymphocytes, monocytes, platelets, and neutrophil/lymphocyte ratio in relation to the control group. Patients had higher levels of C-reactive protein compared to the control group. Determination of the allele frequency and genotypic distribution of the IRF1 polymorphism (rs839) showed a prevalence of the wild-type allele C (65.4%; 62.8%) and CT genotype (48.5%; 52.4%) in patients with SCA and CG, with no statistical difference between groups. Patients with CT and TT genotypes who were not taking hydroxyurea had elevated monocyte and platelet counts compared to the CC genotype. Patients with TT genotype had a higher incidence of cholecystitis compared to CC and CT genotypes. In summary, the study demonstrated an association between the TT genotype of the IRF1 polymorphism (rs839) with elevated monocyte and platelet counts, and a history of cholecystitis in patients with SCA, highlighting its association with poor prognosis. However, studies with larger sample sizes are necessary to confirm these findings.