title: Polymorphisms in TNF and IFNG are associated with clinical characteristics of aplastic anemia in Argentinean population.
abstract: The impaired hematopoiesis in acquired aplastic anemia (AA) results from immune-mediated mechanisms. We characterized polymorphisms implicated in controlling type-1 cytokine production in 69 patients with AA. Our data suggest that the studied polymorphisms are not associated with susceptibility in the overall AA population. However, the presence of the higher expressing TNF - 308A allele was associated with younger age (p = 0.0297) and more profound neutropenia (p = 0.0312), and over-represented in patients with very severe AA (p = 0.0168). The higher producing IFNG 12 CA-repeat allele showed strong linkage disequilibrium with the + 874T allele, and was associated with a lower hemoglobin level (p = 0.0351). Also, the presence of at least one higher expressing variant was more frequent among patients responding to immunosuppressive treatment (p = 0.0519). Our findings suggest that the presence of higher expressing variants of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in AA patient genotypes could be related to clinical parameters, disease severity and therapy outcomes.
authors.affiliation: Laboratorio de Genética Hematológica, Instituto de Medicina Experimental (IMEX)-CONICET/Academia Nacional de Medicina, Ciudad Autónoma de Buenos Aires , Argentina.
authors.forename: Yesica
authors.initials: Y
authors.lastname: Bestach
authors.forename: Yamila
authors.initials: Y
authors.lastname: Sieza
authors.forename: Myriam
authors.initials: M
authors.lastname: Attie
authors.forename: Cecilia
authors.initials: C
authors.lastname: Riccheri
authors.forename: Verónica
authors.initials: V
authors.lastname: Verri
authors.forename: Moira
authors.initials: M
authors.lastname: Bolesina
authors.forename: Raquel
authors.initials: R
authors.lastname: Bengió
authors.forename: Irene
authors.initials: I
authors.lastname: Larripa
authors.forename: Carolina
authors.initials: C
authors.lastname: Belli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000235:genetics* / Q000473:pathology; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001118:Argentina; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D018900:Dinucleotide Repeats / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016572:Cyclosporine
keywords: IFNG; TNF; Tumor necrosis factor-α; aplastic anemia; interferon-γ; polymorphisms