Background: β-thalassemia major (β-TM) is a severe transfusion-dependent anemia driven by excess free α-globin–mediated oxidative stress and ineffective erythropoiesis. Alpha-hemoglobin stabilizing protein (AHSP) binds free α-globin and may modify disease severity. Our objective was to examine the relationship between the disease severity and AHSP rs4499252 (A/G) in a group of β-TM children from Egypt.
Patients and methods: A case control study was performed on 70 patients with β-TM and 30 age- and sex-matched healthy controls. Clinical data, hematological and biochemical profiles were obtained. AHSP rs4499252 was genotyped by real-time PCR.
Results: The G allele and AG/GG genotypes of AHSP rs4499252 were significantly overrepresented in patients and were strongly associated with β-TM (AG: OR = 3.64; GG: OR = 10.19) in dominant and recessive models. Within the patient group, mutant genotypes were linked to lower steady-state hemoglobin and a higher likelihood of moderate–severe disease, and logistic regression confirmed that AG and GG genotypes independently predicted moderate–severe β-TM (AG: OR = 13.27; GG: OR = 29.50), with the G allele also associated with greater severity.