Abstract
Though the patients with sickle cell anemia (SCA) inherit same genetic mutation, they show considerable phenotypic heterogeneity. It has been observed that patients with elevated fetal hemoglobin (HbF) levels have a relatively mild clinical course. There is sparse literature on the association of higher HbF levels leading to reduction in the oxidative stress in SCA patients. Hence in this study, the significance between the HMOX1 gene polymorphisms and the HbF levels has been studied. Preliminary screening was carried out. Genotyping of 3 variants in the HMOX1 gene was performed in 90 SCA patients and 50 healthy controls by PCR–RFLP, GeneScan and direct DNA sequencing. It was observed that SCA patients with higher HbF levels, showed improved hematological indices with an inverse effect on HbS levels. The TT genotype of rs2071746 (A→T) polymorphism was found to be associated with elevated HbF levels (P: 0.012). Also, the long form (> 25 GT repeats) of rs3074372 (GT)n repeats was found to be linked with increased HbF levels. We could not find any association of rs2071749 (A→G) polymorphism with the HbF levels. As, the sickle cell anemia patients show significant oxidative stress due to hemolysis, the study of polymorphisms in the HMOX1 gene may act as a potential independent marker for elevated HbF levels.
Highlights
Though the patients with sickle cell anemia (SCA) inherit same genetic mutation, they show considerable phenotypic heterogeneity
The enzyme occurs as 2 isozymes, an inducible heme oxygenase-1 (HO-1) which is induced in presence of free heme and a constitutive heme oxygenase-25
In order to understand the effect of elevated HbF levels on the hematological indices, the patients were classified into 2 groups considering the median HbF levels of 18.1%.It was observed that the hematological indices were significantly improved in patients with higher HbF levels as compared to the other group
Summary
Though the patients with sickle cell anemia (SCA) inherit same genetic mutation, they show considerable phenotypic heterogeneity. Recent studies have shown that increased levels of HbF are associated with significant elevation in the antioxidant enzymes like superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and reduced glutathione (GSH), with an inverse effect on lipid peroxidation, lowering the oxidative stress in the organs and reducing cellular injuries[9,10]. With this background an identification of genetic marker that is involved. In this study we have screened for the 3 polymorphisms in the HMOX1 gene and have evaluated their association of genotypes with the HbF levels in sickle cell homozygous patients
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