title: Clinical importance of transforming growth factor-beta but not of tumor necrosis factor-alpha gene polymorphisms in patients with the myelodysplastic syndrome belonging to the refractory anemia subtype.
abstract: OBJECTIVE
  Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the myelodysplastic syndrome (MDS). There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located in codon 10 in exon 1 and in the -308 promoter region of TNF-alpha. The objective of this study was to investigate the association between TNF-alpha and TGF-beta1 gene polymorphisms and the susceptibility to MDS and the progression of the disease among patients with MDS belonging to the refractory anemia (RA) subtype.
  
  
  METHODS
  The diagnosis of MDS (n = 50) was based on the FAB criteria. The TNF-alpha genotypes were analyzed by PCR-RFLP and the TGF-beta genotypes were analyzed using an amplification refractory mutation system.
  
  
  CONCLUSIONS
  Compared with healthy control subjects, patients with RA showed no significant deviations in genotype or allele frequencies of TNF-alpha. The TT homozygosity at codon 10 of TGF-beta1 was significantly higher among patients with bi- or pancytopenia (severe group) than in the patients with anemia only (mild group; odds ratio = 6.99, p = 0.003). These findings suggest that the TGF-beta1 gene polymorphism in codon 10 and the -308 TNF-alpha gene polymorphism do not predispose to the development of RA, but the TGF-beta1 gene polymorphism may affect disease progression.
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Balog
authors.forename: Zita
authors.initials: Z
authors.lastname: Borbényi
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Gyulai
authors.forename: Lenke
authors.initials: L
authors.lastname: Molnár
authors.forename: Yvette
authors.initials: Y
authors.lastname: Mándi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000753:Anemia, Refractory / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA