Polymorphism of exon 2 in hbb gene in beta thalessemia major children in north karnataka.

Abstract

INTRODUCTION

Beta thalassemia major is a severe genetic blood disorder caused by mutations in the HBB (beta-globin) gene, leading to defective haemoglobin production, chronic anaemia, and severe complications such as growth retardation, splenomegaly, and iron overload due to frequent blood transfusions. It is an autosomal recessive disorder that predominantly affects populations with high rates of consanguinity, including regions like North Karnataka. The management of beta thalassemia major involves lifelong blood transfusions, iron chelation therapy, and, in some cases, hematopoietic stem cell transplantation (HSCT). Despite these therapeutic advancements, a better understanding of the genetic mutations and polymorphisms associated with the disease can help improve treatment strategies, prognosis, and genetic counselling.1 Beta thalassemia is caused by a wide range of mutations in the HBB gene, located on chromosome 11, that disrupt beta-globin chain synthesis. These mutations are highly heterogeneous and vary across different ethnic and geographical populations. While some mutations result in the complete absence (β⁰) of beta-globin production, others lead to a partial reduction (β⁺) in its synthesis. In India, more than 30 common mutations have been reported in beta thalassemia patients, with IVS1-5(G>C), IVS1-1(G>T), and 619-bp deletion being among the most prevalent.2 However, apart from these major mutations, single nucleotide polymorphisms (SNPs) and variations in specific regions such as exon 2 of the HBB gene may also influence the severity and clinical manifestations of the disease. Polymorphisms in the HBB gene, particularly in exon 2, have been of growing interest in recent research. Exon 2 encodes a critical segment of the beta-globin polypeptide chain, and variations in this region may affect haemoglobin function, disease severity, and treatment response. Some polymorphisms might lead to modifications in haemoglobin stability,