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- Title
Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes.
- Authors
Bestach, Yesica; Nagore, Virginia; Flores, María; González, Jacqueline; Arbelbide, Jorge; Watman, Nora; Sieza, Yamila; Larripa, Irene; Belli, Carolina; Nagore, Virginia Palau; Flores, María G; González, Jacqueline
- Abstract
Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (-308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (-174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.
- Subjects
ARGENTINA; GENETIC polymorphisms; BLOOD diseases; BONE marrow diseases; CYTOKINES; CELLULAR immunity; COMPARATIVE studies; DISEASE susceptibility; GENES; INTERLEUKINS; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; MULTIVARIATE analysis; MYELODYSPLASTIC syndromes; RESEARCH; THROMBOCYTOPENIA; TUMOR necrosis factors; EVALUATION research; RETROSPECTIVE studies; SEVERITY of illness index; KAPLAN-Meier estimator; GENOTYPES; DISEASE complications
- Publication
Annals of Hematology, 2017, Vol 96, Issue 8, p1287
- ISSN
0939-5555
- Publication type
journal article
- DOI
10.1007/s00277-017-3036-4