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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.

Abstract：

: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 2-21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha -308G>A gene polymorphism and the presence of α2-thal3.7 kb 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, beta(S)-globin gene haplotypes and α2-thal3.7 kb 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.

journal_name

Cytokine

journal_title

Cytokine

authors

Cajado C,Cerqueira BA,Couto FD,Moura-Neto JP,Vilas-Boas W,Dorea MJ,Lyra IM,Barbosa CG,Reis MG,Goncalves MS

doi

10.1016/j.cyto.2011.07.002

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

312-7

issue

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(11)00220-1

journal_volume

pub_type

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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.