Abstract
Introduction: Sickle Cell Anaemia (SCA) is an inherited disorder characterised by homozygosis for the mutation that causes Haemoglobin S (Hb S) production. SCA patients have increased serum levels of circulating Tumour Necrosis Factor Alpha (TNF-alpha) and Interleukin 8 (IL-8) during crisis events, occasions because of increased production from inflammatory cells, glia and neurons, these inflammatory molecules additionally contribute to the advanced mechanisms concerned in vascular occlusion events.
Aim: This study aimed to investigate polymorphisms in the TNFalpha and IL-8 genes, their association with the haematological changes, to investigate the association between the TNF-alpha and IL-8 gene polymorphisms and the TNF-alpha and IL-8 serum levels in Saudi SCA patients presented with or without treatment in comparison to healthy individuals.
Materials and Methods: The study included 87 SCA patients diagnosed as homozygous for Haemoglobin S (Hb S; using haemoglobin electrophoresis methods and High-Performance Liquid Chromatography (HPLC) and attended at hereditary blood disease centre (Al-Ahsa; Saudi Arabia) for follow-up. The patients of both genders in all age groups were subdivided into two groups; 27 of the patients were undergoing hydroxyurea treatment (AHU) and 60 patients without hydroxyurea treatment against 30 healthy individual setting as control group. The collected data were analysed using the STATA SE 10 and GraphPad Prism 5.0.
Results: TNF-alpha and IL-8 levels were significantly higher within the plasma of SCA individuals compared to control individuals. The GG and AA genotypes of TNF-alpha-308G>A were associated with the increase in the serum levels of TNF-alpha in SCA patients. While, AA and TT genotypes -251A>T IL-8 gene polymorphism was associated with increase in the serum levels of IL-8 in SCA patients.
Conclusion: The haematological investigations of SCA further highlight the contribution of genetic modifications to the risk of clinical genotypes to understand the association of serum levels of TNF-alpha and IL-8 in patients under HU compared to their gene polymorphism.