title: Association of TNF polymorphisms with JAK2 (V617F) myeloproliferative neoplasms in Brazilian patients.
abstract: The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V617F mutation and both TNF polymorphisms using PCR-RFLP. Thirty three (26.8%) patients with polycythemia vera (PV), 35 (28.7%) essential thrombocythemia (ET), 22 (17.7%) primary myelofibrosis (PMF), and 33 (26.8%) with unclassifiable MPN (MPNu) were included in the study. The JAK2 V617F mutation was detected in 94 (76.42%) patients. Were observed a significant increase on the frequency of the TNF-238 GA genotype in MPN patients compared to controls (OR=2.21, 95% CI=1.02-4.80, P<0.04). The distribution of the genotypes and allelic frequencies of TNF-308 was significantly different among the MPNs, JAK2V617F positive, PV and PMF, and controls. Our data has demonstrated that the polymorphisms on TNF-238 GA, TNF-308 GA were associated to MPN development in this population, triggered by JAK2 V617F mutation.
authors: Post Graduation Program of Biosciences and Physiopathology, Biomedicine and Clinical Analysis Department, Maringa State University, Maringa, PR, Brazil.
authors: Luciana Conci
authors: LC
authors: Macedo
authors: Basic Health Sciences Department, Maringa State University, Maringa, PR, Brazil.
authors: Fernanda
authors: F
authors: de Cesare Quintero
authors: Hematologist Hospital Cancer Maringa, Maringa, PR, Brazil.
authors: Sara
authors: S
authors: Pagliari-E-Silva
authors: Centro de Hematologia e Hemoterapia de Campinas, Universidade Estadual de Campinas, São Paulo, Brazil.
authors: Katia Borgia Barbosa
authors: KB
authors: Pagnano
authors: Post Graduation Program of Biosciences and Physiopathology, Biomedicine and Clinical Analysis Department, Maringa State University, Maringa, PR, Brazil.
authors: Camila
authors: C
authors: Rodrigues
authors: Post Graduation Program of Biosciences and Physiopathology, Biomedicine and Clinical Analysis Department, Maringa State University, Maringa, PR, Brazil.
authors: Josiane Bazzo
authors: JB
authors: de Alencar
authors: Basic Health Sciences Department, Maringa State University, Maringa, PR, Brazil.
authors: Ana Maria
authors: AM
authors: Sell
authors: Basic Health Sciences Department, Maringa State University, Maringa, PR, Brazil. Electronic address: jelvisentainer@gmail.com.
authors: Jeane Eliete Laguila
authors: JE
authors: Visentainer
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: BRC-ABL negative; Janus kinase 2; Mutation; Myeloproliferative disorders; Philadelphia chromosome; Tumor necrosis factor-alpha