Polymorphisms in TGFbeta and TNFalpha are associated with the myelodysplastic syndrome phenotype.
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.
Powers
Martin P
MP
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.
Nishino
Ha
H
Luo
Yamin
Y
Raza
Alina
A
Vanguri
Amulya
A
Rice
Lawrence
L
Zu
Youli
Y
Chang
Chung-Che Jeff
CC
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*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha