Comparison between H63D and G71D gene mutation effects on iron overload in Iraqi patients with β-thalassemia major: A case–control study

Abstract

BACKGROUND: Iron overload certainly will develop in β-thalassemia major. Iron homeostasis was mostly regulated by hepcidin that synthesized in the liver and encoded by the hepcidin antimicrobial peptide (HAMP) gene. HAMP and HFE genes, respectively, encode iron-regulating proteins (Hepcidin and HFE). The iron overload's possibility will increase if there is an interaction between β-thalassemia and HAMP-HFE gene mutations. AIM OF STUDY: In β-thalassemia major patients, we need to identify mutations in iron-regulating genes (HAMP and HFE genes), their impact on the iron overload, and their association with some clinicopathological parameters. PATIENTS AND METHODS: During a period of 5 months from (November 2020 to March 2021), a case–control study was conducted. It included 80 patients and controls aged ≥14 years and divided into two groups: thalassemic patient group included 40 patients who were diagnosed by complete blood count, blood film, and hemoglobin – electrophoresis as β-thalassemia major and control group included 40 unrelated, apparently healthy controls that were age and gender matched with thalassemic patient group. Complete blood count, liver and renal function tests, serum ferritin, and DNA extraction were performed. RESULTS: There was a statistically significant difference between study groups by H63D mutations. The proportion of CG genotype was significantly higher among thalassemic patient group than that in controls. There was no statistically significant difference (P = 0.082) between study groups by G71D mutations. Serum ferritin and Alanine transaminase (ALT) levels were significantly higher in patients with CG and GG genotypes compared to that in patients with CC genotype of H63D. CONCLUSION: H63D is associated with iron overload in β-thalassemia patients with unapparent effect on biochemical and hematological data except for ALT and serum ferritin. This could allow early diagnosis and proper treatment to overcome the complications of iron overload in those patients.