Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia
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Date
2020-09-14
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MDPI
Abstract
Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA).We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454,MPO rs2333227) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity
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Keywords
Camille Faes, Indou Déme Ly, Vincent Pialoux, Université Cheikh Anta Diop, ACE: Maternal and Infant Health, sickle cell anemia, hydroxyurea-free, alpha-thalassemia, HbF QTL, G6PD deficiency, clinical severity, oxidative stress parameters, oxidative stress polymorphisms, ACE: Maternal and Infant Health