TY - JOUR
T1 - Polymorphisms in TGFβ and TNFα are associated with the myelodysplastic syndrome phenotype
AU - Powers, Martin P.
AU - Nishino, Ha
AU - Luo, Yamin
AU - Raza, Alina
AU - Vanguri, Amulya
AU - Rice, Lawrence
AU - Zu, Youli
AU - Chang, Chung Che
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=37349027319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37349027319&partnerID=8YFLogxK
M3 - Article
C2 - 18081437
AN - SCOPUS:37349027319
VL - 131
SP - 1789
EP - 1793
JO - Archives of Pathology and Laboratory Medicine
JF - Archives of Pathology and Laboratory Medicine
SN - 0003-9985
IS - 12
ER -