Assessing oxidative stress in foetuses with β-globin gene mutations

Background & objectives Haemoglobinopathies, particularly thalassemia and sickle cell disease, are of major public health concern and pose a significant health burden in India particularly in the State of Odisha. The molecular complexity of β-thalassemia involves over 350 mutations, resulting in reduced beta-globin synthesis, excess iron, and oxidative stress. Methods Chorionic villi samples from β-thalassemia carrier mothers collected through trans-abdominal chorionic villi sampling (TA-CVS) were screened by real-time polymerase chain reaction for the most commonly found β-globin gene mutations: IVS 1-1 (G>T), 619 bp deletion, IVS 1-5 (G>C), CD15 (G>A), FS41/42 (-TTCT), HbS, FS8/9 (+G), -90 (C>T), CD16 (-C), HbE, CD15 (-T), CD30 (G>C), and -28 (A>G) using TOCE™ (Tagging Oligonucleotide Cleavage and Extension) technology. Reduced glutathione (GSH), redox status (GSH/GSSG ratio), and endothelin-1 (ET-1) were investigated in foetuses of defined β-globin gene mutations by colorimetry and ELISA, respectively, to explore the potential of GSH and ET-1 as oxidative stress biomarkers. Results Of the total cases included in this study 40 per cent showed occurrence of HbS mutations with significant differences in GSH, GSSG, and redox ratio among mutation groups (P<0.05). Correlation analysis revealed a non-significant association between GSH and ET-1 levels. Interpretation & conclusions This study provides key insights into oxidative stress in foetuses with defined β-globin gene mutations. GSH and ET-1 may be therapeutic targets to mitigate oxidative stress and healthy placentation in pregnancies with haemoglobinopathies.