Polymorphisms in TGFβ and TNFα are associated with the myelodysplastic syndrome phenotype

Context. - 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 α (TNF-α) and transforming growth factor β (TGF-β) cytokines are overrepresented in a cohort of patients with MDSs. Design. - DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFα and 2 in TGFβ1, 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 TNFα gene and the TGFβ1 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 TNFα and TGFβ1 are overrepresented in the MDS population suggesting that increased TNF-α and TGF-β1 activity may contribute to the susceptibility and/or pathogenesis of MDS. Further studies with larger sample sizes are warranted to confirm our observation.