title: Polymorphisms in TGFbeta and TNFalpha are associated with the myelodysplastic syndrome phenotype.
abstract: BACKGROUND
  Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS.
  
  
  OBJECTIVE
  To determine if certain polymorphisms in the tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) cytokines are overrepresented in a cohort of patients with MDSs.
  
  
  METHODS
  DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFalpha and 2 in TGFbeta1, were determined using single-specific-primer polymerase chain reaction. The allele and genotype frequencies were compared with similar populations in the National Cancer Institute SNP500 database.
  
  
  RESULTS
  In our MDS population, the -308A/A genotype of the TNFalpha gene and the TGFbeta1 allele +29T and genotype +29T/T, each associated with higher levels of expression, were overrepresented in our MDS population.
  
  
  CONCLUSIONS
  Polymorphisms associated with increased expression in the cytokines TNFalpha and TGFbeta1 are overrepresented in the MDS population suggesting that increased TNF-alpha and TGF-beta1 activity may contribute to the susceptibility and/or pathogenesis of MDS. Further studies with larger sample sizes are warranted to confirm our observation.
authors: Department of Pathology and Laboratory Medicine, The Methodist Hospital Research Institute and The Weill Medical College of Cornell University at The Methodist Hospital, Houston, Tex 77030, USA.
authors: Martin P
authors: MP
authors: Powers
authors: Ha
authors: H
authors: Nishino
authors: Yamin
authors: Y
authors: Luo
authors: Alina
authors: A
authors: Raza
authors: Amulya
authors: A
authors: Vanguri
authors: Lawrence
authors: L
authors: Rice
authors: Youli
authors: Y
authors: Zu
authors: Chung-Che Jeff
authors: CC
authors: Chang
mesh_terms: D005787:Gene Frequency; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha