Genotype-Phenotype Study of β-Thalassemia Patients in Sabah

Abstract

β-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 β-globin gene mutations, coinheritance with α-globin gene mutations, XmnI-^Gγ, and rs368698783 polymorphisms on the β-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 β- and α-globin gene mutations, as well as XmnI-^Gγ and rs368698783 polymorphisms. Our data show that the high prevalence of β-thalassemia in Sabah is not due to consanguineous marriages (5.4%). A total of six different β-globin gene mutations were detected, with Filipino β°-deletion being the most dominant (87.4%). There were 77.5% homozygous β-thalassemia patients, 16.2% compound heterozygous β-thalassemia patients, and 6.3% β-thalassemia/Hb E patients. Further evaluation on compound heterozygous β-thalassemia and β-thalassemia/Hb E patients found no concomitant α-globin gene mutations and the rs368698783 polymorphism. Furthermore, the XmnI-^Gγ (−/+) genotype did not demonstrate a strong impact on the disease phenotype, as only two of five patients in the compound heterozygous β-thalassemia group and two of three patients in the β-thalassemia/Hb E group had a moderate phenotype. Our findings indicate that the severity of the β-thalassemia phenotypes is closely related to the type of β-globin gene mutations but not to the XmnI-^Gγ and rs368698783 polymorphisms.

Keywords:

• β-globin gene mutation
• Sabah state
• XmnI-^Gγ polymorphism
• β-thalassemia
• genotype-phenotype

Acknowledgments

We are grateful to the communities and individuals who voluntarily participated in this study. We thank the Medical staff of the Thalassemia Center at the Likas Women and Children’s Hospital for their assistance in sample collection.

Ethical approval

The present study was approved by the Medical Ethics Committee of the Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah [JKEtika3/19(25)] and the Medical Research Ethics Committee of the Ministry of Health (NMRR-19-3525-50523).

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by the Universiti Malaysia Sabah internal grant [GUG0437-1/2020] and Fundamental Research Grant Scheme from the Ministry of Higher Education, Malaysia (FRGS/1/2018/SKK10/UMS/01/1).