BIOCHEMICAL PROFILING AND MOLECULAR CHARACTERIZATION OF BETA GLOBIN GENE OF BETA THALASSEMIA MAJOR PATIENTS IN PUNJAB, PAKISTAN
Keywords:
Beta thalassemia, β-globin, biochemical profiling, molecular characterization IntroductiAbstract
Beta thalassemia major is a fatal genetic blood disorder that gets transferred from parents to the next generation while the parents being the only carriers don’t face any clinical complications. However, the thalassemia major patients remain blood transfusion-dependent throughout their lives and that becomes a reason for oxidative stress in their body leading to more complications. These clinical complications need to be monitored regularly to refrain from further problems and early death of patients. Blood samples of patients were collected for DNA isolation and biochemical profiling. Primers were designed using Primer3plus and verified by in-silico PCR. The secondary structures of proteins were obtained via Psipred by using obtained sequences of samples. TrRosetta software was used to predict the 3D structure of amplified protein and AutoDockvina was used to predict the interactions between protein and ligands i.e. Folic acid and vitamin D3. A total of 91 beta thalassemia major patients were included in this study. Basic demographic details along with their biochemical profiles were collected from patients and the Fatimid Foundation. Statistical analysis showed a statistically non-significant correlation between the levels of ALT, AST, ALP and Hb i.e. p= 0.149, p= -0.161 and p= 0.062 respectively. The primer for 3rd exon of beta globin gene was used to amplify the selected exonic regions. The predicted secondary structures obtained by Psipred were used to compare the helix and coils of mutant protein with wild and it showed significant differences. The predicted secondary 3D structures obtained by trRosetta were used to check molecular interaction between beta globin and ligands. The molecular interaction between folic acid and beta globin gene showed the affinity of -4.4 kcal/mol and the interaction of vitamin D3 and beta globin showed the affinity of -4.6 kcal/mol. These interactions show very weak binding between the ligand and protein which confirms that the health complications faced by beta thalassemia major patients aren’t sufficiently dealt by using these supplements. This study is an attempt to understand the health complications faced by beta thalassemia patients and the results can be used for designing personalized drugs for the patients.
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