Association of heme oxygenase-1 hmox-1 gene polymorphism with sickle cell disease in egyptian patients

Background: Sickle Cell Disease (SCD) is a monogenic disorder characterized by a diversity of phenotypic presentations that could be attributed to genetic variations. Heme Oxygenase-1 (HO-1) enzyme acts as a cytoprotective enzyme in the human body; thus, it is viewed as the rate-limiting enzyme responsible for the catabolism of heme and the release of metabolites which have antioxidant and anti-inflammatory effects. Accordingly, we hypothesized that Heme Oxygenase-1 (HMOX-1) geneA>Tpromoter polymorphism (rs2071746) may influence the clinical and laboratory features of SCD and may as well have an association with the variable severity of the disease itself. Subjects and Methods:A cohort of 100 patient with Sickle cell disease and 100 healthy controls were enrolled in this case control study.Genotyping of HMOX-1 gene A>T promoter polymorphism (rs2071746) was performed using taqman Real-Time polymerase chain reaction assay. Results: A significant association between the HMOX-1 gene homozygous TT genotype and pulmonary dysfunction in studied patients with SCD was found. Conclusion: Our observations suggest that the HMOX-1 gene A>T promoter polymorphism and a subsequent deficient HO-1 response may play a role in exposing SCD patients to the damaging effects of excess heme released by high rates of chronic red blood cell sickling and lysis. Moreover, variable HO-1 response may be associated with the diverse severity of some SCD complications, such as pulmonary dysfunction including Acute Chest Syndrome (ACS) and Pulmonary Hypertension (PHT).