TNF-alpha and IL-8: Serum levels and gene polymorphisms (−308G>A and −251A>T) are associated with classical biomarkers and medical history in children with sickle cell anemia
| Autor: | Cynara Gomes Barbosa, J.P. Moura-Neto, Cyntia Cajado, Marilda Souza Goncalves, Isa Menezes Lyra, Wendell Vilas-Boas, M.J. Dorea, Bruno A. V. Cerqueira, F. D. Couto, Mitermayer G. Reis |
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| Jazyk: | angličtina |
| Předmět: |
Adult
Adolescent Anemia Immunology Enzyme-Linked Immunosorbent Assay Anemia Sickle Cell Biology Biochemistry Polymerase Chain Reaction medicine Immunology and Allergy Humans Allele Child Medical History Taking Molecular Biology Alleles betaS-globin Gene haplotypes Polymorphism Genetic IL-8 Tumor Necrosis Factor-alpha Haplotype Interleukin-8 Case-control study Hematology medicine.disease Sickle cell anemia Cross-Sectional Studies Haplotypes Case-Control Studies Child Preschool Hemoglobin F alpha2-Thalassemia Gene polymorphism Restriction fragment length polymorphism Biomarkers Polymorphism Restriction Fragment Length TNF-alpha |
| Zdroj: | Cytokine. (2):312-317 |
| ISSN: | 1043-4666 |
| DOI: | 10.1016/j.cyto.2011.07.002 |
| Popis: | Sickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) −308G>A and Interleukin 8 (IL-8) −251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2–21years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5years of age. The A allele of the TNF-alpha −308G>A gene polymorphism and the presence of α2-thal3.7kb were associated with an increase risk of splenic sequestration events (p=.001; p=.046), while the T allele of the IL-8 −251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p=.032). Moreover, the A allele of the TNF-alpha −308G>A gene polymorphism was associated with high TNF-alpha levels (p=.021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, betaS-globin gene haplotypes and α2-thal3.7kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcome. |
| Databáze: | OpenAIRE |
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