Iron, Oxidative Stress, and Haptoglobin Gene Polymorphism in Sickle Cell Disease Patients With Inflammation in...

The more severe forms of sickle cell disease (SCD) are highly inflammatory genetic disorders that cause significant oxidative stress. To fight against the free radicals produced, the body has an antioxidant system. In addition, haptoglobin has been reported in several studies as possessing oxidant and inflammatory properties depending on the nature of the genotype. This study hypothesizes that the HP2 allele of haptoglobin may exacerbate oxidative stress in sickle cell patients with inflammation.

An analytical cross-sectional study was conducted for 6 months. The patients recruited were those with severe forms of sickle cell anemia, regularly followed at the hematology department of the Yaoundé Central Hospital and the Bafoussam Regional Hospital. The Public Health Research Biotechnology Laboratory (LAPHER-Biotech) in Yaoundé provided a framework for genotyping haptoglobin by allele-specific PCR. Next, iron, oxidative stress, and inflammatory parameters were assessed by standard methods, and the statistical software R Version 4.1.1. allowed for the data analysis.

Samples from 149 participants were analyzed. Patients with Hp phenotypes 2-2 had a considerable elevation of reduced glutathione (14.3 μmol/L) compared to those of phenotype Hp 2-1 (11.2 μmol/L) and genotype Hp 1-1 (11.8 μmol/L) (p = 0.075). Malondialdehyde was significantly higher in patients with Hp phenotypes 2-2 compared to those with Hp phenotype 2-1 and Hp phenotype 1-1 (p = 0.008). The oxidative stress index (OSI) was higher in patients with the Hp 2-2 phenotype than those with the Hp 2-1 and Hp 1-1 phenotypes (p = 0.008) suggesting that they are more affected by oxidative stress.

This study supports the hypothesis that the Hp 2-2 phenotype of haptoglobin is associated with an imbalance in the oxidative balance in favor of oxidants, suggesting that the latter is a major contributor to the worsening pathophysiology of SCD.