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• W2271934910 abstract "Abstract Introduction Idiopathic acquired aplastic anemia (AAA) is a rare and life-threatening disease, characterized by pancytopenia. Its immune-mediated physiopathology is not yet fully understood. However, important associations have been reported in AAA, which include the association with certain HLAs, the presence of a PNH clone in 40-50% of cases, occurrence of a hepatitis associated variant in about 5-10% of cases, the occurrence of interferon gamma (IFN-g) and tumor necrosis factor alpha (TNF-a) producing T cells in the peripheral blood and bone marrow cells. Not much is known about cytokine gene polymorphisms in AAA and its relationship with HLA alleles. The IFN-γ +874 A/T gene polymorphism, and specially the +874TT genotype, have been associated with elevated levels of IFN-γ production. The individuals can present 3 different phenotype (TT, TA or AA). Some groups have demonstrated that the TT (the IFN-gamma “hyper-producer type”) is possibly overrepresented in AA patients and correlates with susceptibility to the disease. In order to better understand the relationship between these immune parameters, we investigated the associations between IFN-g gene polymorphism in AAA patients and its relationship with the presence of HLADR15 (identified as of greater importance in our local patients). Materials and methods In this study we analyze the variations of the gene polymorphism at position +874 interferon in 30 consecutive patients with confirmed diagnosis of AAA,in 2012 and 2013, at the Federal University of the State of Bahia Hospital/Brazil. Diagnosis of AAA was confirmed by bone marrow biopsy. Patients also had their HLA typing and were tested for the IFN-gamma gene polymorphism at +874 T/A position using the ARMS methodology described by Pravica. As controls, 116 healthy individuals from the same population (Bahia/Brazil) were tested for these polymorphism. The analysis of the association between the gene polymorphism and the chances of developing AAA, and the polymorphism and the HLA-DR15, were performed using qui-square/exact fisher test. The results were expressed as OR. Results We have found genotypic frequency of the A allele in 65%(n=39/60) in the aplastic patients (control 64.2%, n = 232, OR 1.05, p=0.87). The T allele was found in 35%(n =21/60)of the cases (control 34.6%, OR 0.95, p=0.87). Thus, there was no difference between the genotypic frequency of the alleles among patients with aplasia and the control group. In addition, there was NO difference between the frequency of the phenotype (TT, AT or AA) between patients with AAA and control group, respectively 16,5%, 36,5%, 46% (AAA, n =30) versus 18.1% , 35.3%, 46.6% (n = 116 control) (p=n.s.). The association of the polymorphism was tested and compared to the HLA-DR15. There was NO association between the IFN-gamma gene polymorphisms and the presence of HLADR15 (p =,90). Conclusion In our brazilian cohort, the +874 T/A IFN-gamma gene polymorphism was Not associated with the onset of AAA. Also, there was No association between IFN-gamma gene polymorphism and the antigen HLA-DR15. TT phenotype, possibly the predisposing one for disease, was expressed only in 15% of patients with AAA. These findings corroborate the presence of a much more complex pathogenesis in AAA ,and that, regional differences in genetic and immune mechanisms may co-exist. Disclosures: No relevant conflicts of interest to declare." @default.
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• W2271934910 date "2013-11-15" @default.
• W2271934910 modified "2023-09-26" @default.
• W2271934910 title "The Interferon Gamma Gene Polymorphism In Acquired Aplastic Anemia and Its Association With HLA" @default.
• W2271934910 doi "https://doi.org/10.1182/blood.v122.21.1236.1236" @default.
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