Assessing oxidative stress in foetuses with β-globin gene mutations

Area of Science:

• Genetics and Molecular Biology
• Hematology
• Reproductive Medicine

Background:

• Haemoglobinopathies like thalassemia and sickle cell disease are significant public health issues in India.
• Over 350 mutations in the beta-globin gene cause β-thalassemia, leading to excess iron and oxidative stress.
• Odisha, India, faces a substantial health burden from these genetic blood disorders.

Purpose of the Study:

• To investigate oxidative stress biomarkers in fetuses with defined beta-globin gene mutations.
• To explore the potential of reduced glutathione (GSH) and endothelin-1 (ET-1) as indicators of fetal oxidative stress.
• To understand the molecular complexity and health implications of beta-thalassemia and sickle cell disease.

Main Methods:

• Screening of beta-globin gene mutations (e.g., IVS 1-1, HbS, HbE) in chorionic villi samples using real-time PCR and TOCE™ technology.
• Quantification of reduced glutathione (GSH) and the GSH/GSSG redox ratio via colorimetry.
• Measurement of endothelin-1 (ET-1) levels using ELISA in fetuses with identified beta-globin gene mutations.

Main Results:

• Forty percent of cases exhibited HbS mutations, with significant differences in GSH, GSSG, and redox ratio across mutation groups (P<0.05).
• A non-significant correlation was observed between GSH and ET-1 levels.
• Identified specific beta-globin gene mutations and their association with oxidative stress markers.

Conclusions:

• Provides critical insights into fetal oxidative stress associated with defined beta-globin gene mutations.
• Reduced glutathione (GSH) and endothelin-1 (ET-1) may serve as valuable therapeutic targets.
• Potential to mitigate oxidative stress and promote healthy placentation in pregnancies affected by haemoglobinopathies.