Detection of BCL11A and HMIP Polymorphisms among Anemic Patients with Elevated HbF in Hospital Universiti Sains Malaysia

Abstract

Anemia is a condition that is usually associated with a variety of diseases. For normal adults, the level of fetal hemoglobin (HbF) is less than 1.0%, which is influenced by several genetic loci. Objectives: To determine the association between elevated HbF level and the presence of rs1186868 and rs9376090 polymorphism in anemic patients due to acquired causes. Methods: This study involved 144 anemic patients with HbF level ≥1.0%. High-Performance Liquid Chromatography (HPLC) was used to determine the HbF and HbA2 level. Multiplex ARMS-PCR and Gap-PCR were performed for those samples with high HbA2 level (>3.2%) and normal HbA2 level (≤3.2%) to detect mutation and deletion at β-globin gene cluster, respectively. Allelic discrimination for rs1186868 and rs9376090 were performed using real-time PCR for samples with no mutation and deletion. Results: The mean age of patients is 19.99±1.64 year with 61.1% female predominance. The majority of the patients were Malays (99.3%). There was a moderate negative correlation and statistically significant difference between HbF level and Hb level, (r=-0.348, P<0.05) while the correlation between HbF level with MCV and MCH showed weak negative correlation but was not statistically significant, (r=-0.079, P>0.05) (r=-0.072, P>0.05). The minor allele frequency (MAF) in both rs1186868 and rs93760890 for HbF>1.0% patients showed similarity with East Asian (EAS) population. Conclusion: This finding shows the presence of rs1186868 and rs9376090 SNPs in Malaysian population and emphasising the need for further functional studies to confirm the association between these SNPs with HbF hence, could provide better approach in management of anemic patients.