OMICS of Beta Thalassemia: Review Article - Abstract
Background: Beta - Thalassemia is the most common hemoglobinopathy throughout the world. Beta globin chain synthesis is completely or partially compromised in the affected individuals. This leads to transfusion dependency in majority of patients. However, despite of genetically proven beta thalassemia major transfusion requirement in some patients is negligible or seldom required.
Introduction: Around 400 mutations have been identified till now, among which five to six are common in a certain region. For example IVSI-5(G-C) is commonest mutation in the subcontinent. These mutations act as the primary modifiers. For example mutations in the promoter region lead to less severe disease phenotype while on the other hand, deletions or frame shifts result in severe phenotype. Similarly there are secondary genetic modifiers that are polymorphisms that can modify the phenotype. Xmn1 polymorphism, BCL 11 gene polymorphisms, co inheritance of alpha thalassemia are the well-studied examples. These polymorphisms are associated with increased Hb F especially under stressful conditions like pregnancy, severe anemia, etc. Hb F is the major hemoglobin in the fetal life due to hypomethylated Cp G islands of beta and gamma genes while they become methylated in adult life leading to switching of Hb class. This was the basis of trials of different Hb F augmenting agents. Different studies have shown that individuals harboring certain (IVSI-1, IVSI-5, CD 30, CD 15, etc) primary and secondary modifiers (Xmn1 polymorphism, BCL polymorphism) show promising results with Hb F augmenting agents. These genetic factors can help to formulate the management of thalassemia patients without or with minimum blood transfusions.
Conclusion: Genetic studies of beta Thalassemia patients should be performed as it can help in planning the long term management of these patients. Patients harboring certain primary and secondary genetic modifiers can be managed without blood transfusion