Genetic variants of HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers co-inherited with −α3.7 deletion thalassaemia

Abstract Purpose Filipino β0-deletion is a rare extensive deletion of β-globin gene, which predominantly found in β-thalassaemia patients in the indigenous population of Sabah, Malaysia particularly Kadazandusuns. Co-inherited of Filipino β0-deletion and −α3.7 deletion was commonly found among Kadazandusuns with milder clinical symptoms. Additionally, HBS1L-MYB, an important key regulator in haematopoiesis and erythropoiesis is strongly associated with the variation of HbF levels with milder clinical manifestation. Thus, this study investigates the influence of genetic variants in HBS1L-MYB on Hb subtypes level among thalassaemia carriers co-inherited with Filipino β°-deletion and −α3.7 deletion. Methods Gap polymerase chain reactions (gap-PCRs) were conducted to identify Filipino β0-deletion and −α3.7 deletion. Hb subtypes levels were quantified using BioRad Variant II Hb analyser. Two HBS1L-MYB intergenic polymorphisms (HMIPs)(rs9399137 and rs11759553) were genotyped using in house designed tetra primer ARMS-PCR. Confirmation of HMIPs were done through sequencing. Results Hundred and fifty-seven Filipino β°-deletion carriers from the Kadazandusun were recruited for this study. Out of 157 carriers, thirty-four Filipino β°-deletion thalassaemia carriers were detected for co-inheritance with −α3.7 deletion. The minor allele frequencies (MAF) of the two HMIPs were found more than 0.05 (rs11759553, MAF = 0.18 and rs9399137, MAF = 0.15). For rs11759553, genotypes AT and TT were found with significantly higher HbF level (p = .001). For rs9399137, C allele was found with higher HbF level but no significant difference between different genotypes. Both variants did not influence on the HbA and A2 level. Conclusions Both HMIPs rs11759553 and rs9399137 were significant polymorphisms among thalassaemia carriers co-inherited with Filipino β°-deletion and −α3.7 deletion carriers. Both HMIPs demonstrate higher expression of HbF level.