Gene expression of ALAS2 in patients with iron deficiency anemia: a Case-Control study in Najaf Governorate, Iraq
Keywords:
Gene expression, ALAS2, iron deficiency anemiaAbstract
Background: IDA (iron deficiency anemia) is a major public health issue that is very common in underdeveloped countries. It occurs if the number of erythropoiesis is inhibited due to insufficient iron needed for hemoglobin synthesis. The molecular etiology of anemia may be related to modulation in expression of the erythroid-specific gene aminolevulinate synthase 2 (ALAS2) required for heme biosynthesis.
Present study aims comparison of ALAS2 gene expression levels between healthy persons in Najaf Governorate/Iraq and patients with iron deficiency anemia organisms during the period from August 2025 to February 2026.
Methodology: In the case-control study, 100 patients were included consisting of 50 IDA patients (cases) and 50 healthy age- and gender-matched controls. The clinical and hematological data of all individuals were recorded. Peripheral blood samples were collected for the iron profile and full blood count. Total RNA was isolated from whole blood, and hybrid DNA (cDNA) were prepared. The ALAS2 gene expression was quantified using RT-qPCR followed by the 2^-ΔΔCt method with a housekeeping gene as a reference. We performed statistical analysis to make group comparisons and correlation analyses between gene expression and hematological parameters.
Results: Compared to the controls, patients with IDA clearly had lower hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), serum ferritin and serum iron levels and significantly higher TIBC (P <0.001). This showed a significant downregulation in the expression of ALAS2 gene with IDA patients (mean fold change: 0.45 ± 0.20) compared to controls (1.00 ± 0.30) (P < 0.001). ALAS2 expression correlated
positively with hemoglobin, ferritin, MCV, and MCH (r = 0.58, r = 0.65, r = 0.49 and r = 0.44 respectively) while TIBC showed negative correlation (r =−0.46). Regression analysis further revealed that hemoglobin levels were independently predicted by ALAS2 expression. The diagnostic performance was good with the area under receiver operating characteristic (ROC) curve being the 0.81 as per ROC analysis.
Conclusions: The data show that iron deficiency anemia is associated with a profound decrease in ALAS2 gene expression that correlates closely with the haematological and total body indices of iron in patients. These findings give insight into the pathophysiology of IDA, and strengthen the hypothesis for ALAS2 to be a molecular marker for dysfunctional erythropoiesis. Genomic expression, biomarkers, erythropoiesis and heme production, iron deficiency anemia, ALAS2
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