Deciphering the Genetic Landscape: Exploring the Relationship Between HLA-DQA1, HLA-DQB1, and HLA-DRB1 Genes in Diabetes Mellitus

Abstract

Abstract: Diabetes mellitus (DM) is a complex and multifactorial metabolic disorder with a significant genetic component. The human leukocyte antigen (HLA) genes, specifically HLA-DQA1, HLA-DQB1, and HLA-DRB1, have been implicated in the susceptibility and pathogenesis of DM. This review delves into the intricate interplay of these HLA genes, seeking to unravel the genetic tapestry that contributes to the development and progression of diabetes. We begin by providing an overview of the HLA system and its critical role in immune regulation. Subsequently, we explore the current state of knowledge regarding the association between HLA-DQA1, HLA-DQB1, and HLADRB1 polymorphisms and susceptibility to both type 1 and type 2 diabetes. Emphasis is placed on recent advancements in genetic research methodologies, including genomewide association studies and next-generation sequencing, that have provided deeper insights into the genetic architecture of DM. The review also scrutinizes the functional implications of specific HLA alleles in modulating immune responses and the potential mechanisms by which they contribute to the autoimmune processes observed in type 1 diabetes. Additionally, we examine the role of HLA genes in the context of insulin resistance and beta-cell dysfunction in type 2 diabetes, shedding light on the shared and distinct genetic underpinnings of these two major forms of DM. Furthermore, we discuss the clinical implications of HLA genotyping in predicting disease risk, prognosis, and personalized treatment strategies. The integration of genetic information into clinical practice holds promise for precision medicine approaches in diabetes management.