Clinical Importance of Transforming Growth Factor-β but Not of Tumor Necrosis Factor-α Gene Polymorphisms in Patients with the Myelodysplastic Syndrome Belonging to the Refractory Anemia Subtype

Abstract

Objectives: Tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) are cytokines that play key roles in the myelodysplastic syndrome (MDS). There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-β1 protein, located in codon 10 in exon 1 and in the –308 promoter region of TNF-α. The objective of this study was to investigate the association between TNF-α and TGF-β1 gene polymorphisms and the susceptibility to MDS and the progression of the disease among patients with MDS belonging to the refractory anemia (RA) subtype. Methods: The diagnosis of MDS (n = 50) was based on the FAB criteria. The TNF-α genotypes were analyzed by PCR-RFLP and the TGF-β genotypes were analyzed using an amplification refractory mutation system. Results and Conclusions: Compared with healthy control subjects, patients with RA showed no significant deviations in genotype or allele frequencies of TNF-α. The TT homozygosity at codon 10 of TGF-β1 was significantly higher among patients with bi- or pancytopenia (severe group) than in the patients with anemia only (mild group; odds ratio = 6.99, p = 0.003). These findings suggest that the TGF-β1 gene polymorphism in codon 10 and the –308 TNF-α gene polymorphism do not predispose to the development of RA, but the TGF-β1 gene polymorphism may affect disease progression.