Genotype-Phenotype Study of beta-Thalassemia Patients in Sabah

beta-thalassemia is a serious public health problem in Sabah due to its high prevalence. This study aimed to investigate the effects of different types of beta-globin gene mutations, coinheritance with alpha-globin gene mutations, XmnI-(G)gamma, and rs368698783 polymorphisms on the beta-thalassemia phenotypes in Sabahan patients. A total of 111 patients were included in this study. The sociodemographic profile of the patients was collected using a semi-structured questionnaire, while clinical data were obtained from their medical records. Gap-PCR, ARMS-PCR, RFLP-PCR, and multiplex PCR were performed to detect beta- and alpha-globin gene mutations, as well as XmnI-(G)gamma and rs368698783 polymorphisms. Our data show that the high prevalence of beta-thalassemia in Sabah is not due to consanguineous marriages (5.4%). A total of six different beta-globin gene mutations were detected, with Filipino beta & DEG;-deletion being the most dominant (87.4%). There were 77.5% homozygous beta-thalassemia patients, 16.2% compound heterozygous beta-thalassemia patients, and 6.3% beta-thalassemia/Hb E patients. Further evaluation on compound heterozygous beta-thalassemia and beta-thalassemia/Hb E patients found no concomitant alpha-globin gene mutations and the rs368698783 polymorphism. Furthermore, the XmnI-(G)gamma (-/+) genotype did not demonstrate a strong impact on the disease phenotype, as only two of five patients in the compound heterozygous beta-thalassemia group and two of three patients in the beta-thalassemia/Hb E group had a moderate phenotype. Our findings indicate that the severity of the beta-thalassemia phenotypes is closely related to the type of beta-globin gene mutations but not to the XmnI-(G)gamma and rs368698783 polymorphisms.