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

Martin P. Powers, Ha Nishino, Yamin Luo, Alina Raza, Amulya Vanguri, Lawrence Rice, Youli Zu, Chung Che Chang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1789-1793
Number of pages5
JournalArchives of Pathology and Laboratory Medicine
Volume131
Issue number12
StatePublished - 1 Dec 2007

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Myelodysplastic Syndromes
Phenotype
Cytokines
Genotype
Population
Tumor Necrosis Factor-alpha
National Cancer Institute (U.S.)
Hematopoiesis
Transforming Growth Factors
Gene Frequency
Sample Size
Genes
Bone Marrow
Alleles
Observation
Databases
Apoptosis
Polymerase Chain Reaction
DNA

Cite this

Powers, M. P., Nishino, H., Luo, Y., Raza, A., Vanguri, A., Rice, L., ... Chang, C. C. (2007). Polymorphisms in TGFβ and TNFα are associated with the myelodysplastic syndrome phenotype. Archives of Pathology and Laboratory Medicine, 131(12), 1789-1793.
Powers, Martin P. ; Nishino, Ha ; Luo, Yamin ; Raza, Alina ; Vanguri, Amulya ; Rice, Lawrence ; Zu, Youli ; Chang, Chung Che. / Polymorphisms in TGFβ and TNFα are associated with the myelodysplastic syndrome phenotype. In: Archives of Pathology and Laboratory Medicine. 2007 ; Vol. 131, No. 12. pp. 1789-1793.
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abstract = "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.",
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Powers, MP, Nishino, H, Luo, Y, Raza, A, Vanguri, A, Rice, L, Zu, Y & Chang, CC 2007, 'Polymorphisms in TGFβ and TNFα are associated with the myelodysplastic syndrome phenotype', Archives of Pathology and Laboratory Medicine, vol. 131, no. 12, pp. 1789-1793.

Polymorphisms in TGFβ and TNFα are associated with the myelodysplastic syndrome phenotype. / Powers, Martin P.; Nishino, Ha; Luo, Yamin; Raza, Alina; Vanguri, Amulya; Rice, Lawrence; Zu, Youli; Chang, Chung Che.

In: Archives of Pathology and Laboratory Medicine, Vol. 131, No. 12, 01.12.2007, p. 1789-1793.

Research output: Contribution to journalArticle

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 - 2007/12/1

Y1 - 2007/12/1

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.

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