The large clinical spectrum of Haemoglobin E (HbE)/β-thalassaemia leads to identification of modifiers that cause the complexity1. IGSF4, a member of the immunoglobulin superfamily 4 is known as a thalassaemia-related gene that plays an important role in globin synthesis. Methylation of IGSF4 was reported to interrupt the process of globin synthesis through its interaction with other genes in the regulation network of globin expression2. Specific cells isolation is needed in order to study the methylation profile as the interaction between various haematopoietic cells including nucleated red blood cells (NRBCs) in whole blood could impact the methylation results3. Therefore, the objective of this study was to describe the pattern of DNA methylation at the promoter region of IGSF4 gene that may involve in the alteration of globin synthesis in HbE/β-thalassaemia patients.