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.

Frequencies of -308G/A (TNFA) and -509C/T (TGFB1) polymorphisms in sickle cell anemia patients from Brazil

“…For the -308G/A (TNFA) polymorphism, the frequencies obtained were similar to those results of other SCA studies in Brazil (Cajado et al, 2010;Vicari et al, 2011). Our results also did not differ from those found for the Brazilian population without hemoglobinopathies (Cajado et al, 2011), suggesting that the inheritance of the polymorphisms studied is independent of the β S gene inheritance. In re-lation to the Indian population, the frequencies found in our population did not differ (Ghosh et al, 2010), probably due to the ethnic heterogeneity of both.…”

Comment on “Influence of βS-globin haplotypes and hydroxyurea on tumor necrosis factor-alpha levels in sickle cell anemia”✩✩See paper by Laurentino MR et al. on pages 121-5.

“…As previously reported by the same research group 14 and by other studies,15., 16., 17. TNF-α levels are increased in SCA. This important finding supports the association between pro-inflammatory cytokine release and the clinical severity of SCA as these cytokines induce adhesion molecule activity in the endothelium 18 .…”

Evaluation of high performance liquid chromatography (HPLC) pattern and prevalence of beta-thalassaemia trait among sickle cell disease patients in Lagos, Nigeria

“…Haematological characteristics and clinical severity of SCD are heterogeneous and are associated with environmental and genetic factors that include variation in HbF level, the haplotype locale that is linked to the β-globin gene and the co-inheritance of - α-thalassaemia and other Hb variants [9]. Full blood count and the red cell indices are essential in the preliminary investigation of haemoglobinopathies.…”