The effect of modifier genes on foetal Haemoglobin in the Maltese population

Abstract

Haemoglobinopathies are a set of single-gene disorders that can be inherited throughout affected families. Such genetic diseases affect the correct formation and synthesis of the haemoglobin molecule. Various studies on patients with Hereditary Persistence of Foetal Haemoglobin (HPFH) have shown that three important genes, the cMYB proto-oncogene, the EKLF gene and the BCLJJA gene have a considerable impact in the regulation and control of foetal haemoglobin (HbF). Augmenting the level of HbF in sickle cell disease or β-thalassemia patients would greatly ameliorate the symptoms associated with these diseases. This can only be achieved by first understanding the genetic switch from foetal to adult haemoglobin that is commonly referred to as γ to β globin gene switching. In this study a combination of clinical research coupled with basic research was carried out. 22 β- thalassemia homozygotes and compound heterozygotes were recruited during the follow up clinical visits at the Thalassaemia and Molecular Genetics Clinic, Mater Dei Hospital, Malta. A complete blood count accompanied all blood samples to the laboratory. HbF and HbA2 measurements were conducted using a High-Pressure Liquid Chromatography. DNA genotyping of all samples was performed by TaqMan assays for HBSIL-MYB and BCLIJA polymorphisms. The results showed that even though HBSIL-MYB and BCLIIA are important HbF modifier genes, they do not explain the current HbF heterogeneity in the Maltese β thalassaemia patients. There was however a strikingly positive association between the BCL11A gene and reticulocyte count in Maltese female β thalassaemia patients that varied according to the mutant allele. Even though BCLIIA and HBSJL-MYB failed to reach a level of significance in this study, one must not completely omit further extension of the current work such as extending haplotypes in BCLJJA that surely warrant further investigation regarding their role in globin gene switching.