IDENTIFICATION AND CHARACTERIZATION OF GENETIC VARIANTS ASSOCIATED WITH HUMAN DISEASE SUSCEPTIBILITY

Abstract

Background: β-thalassemia is one of the most significant inherited blood disorders in Pakistan and there is significant sequence variation in HBB gene. It is crucial to characterize these variants to gain insight into disease patterns and help enhance molecular diagnosis and prevention.

Aim: The aim of this study was to find and characterize the variants in HBB gene in patients with beta-thalassemia and investigate their relationship with demographic and clinical features.

Method: The study design was quantitative, multicenter cross-sectional study on 300 adults who were diagnosed with β-thalassemia in four government hospitals of Rawalpindi, Lahore, Peshawar and Faisalabad. Participants were selected using purposive sampling method. Details were gathered on clinical and demographic data and peripheral blood samples were examined for HBB variants using molecular genetic techniques.

Results: Five major HBB variants were identified – deletion of 619 bp, G>C in IVS-I-5, G>T in IVS-I-1, frameshift 41/42 (-TTCT), and frameshift 8/9 (+G). Ethnicity (p=.001), family history (p=.006), consanguinity (p=.002), disease phenotype (p=.017) and transfusion history (p=.038) were significant associations with genetic variation. There was also a significant difference in age at diagnosis (p=.040) and transfusion frequency (p=.007) between the genetic groups, but no significant difference was found for sex, age, duration of transfusion therapy or splenectomy.

Conclusion: Results reveal high level of HBB genetic diversity among patients with β-thalassemia in Pakistan and emphasize importance of molecular characterization for genetic counseling and carrier screening and for the management of the disease.