Arumugam Thilona, Adimulam Theolan, Gokul Anmol, Ramsuran Veron
School of Laboratory Medicine, Medical Science, University of KwaZulu-Natal, Durban, South Africa.
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
Front Immunol. 2024 Sep 17;15:1422834. doi: 10.3389/fimmu.2024.1422834. eCollection 2024.
Variation within the non-coding genome may influence the regulation and expression of important genes involved in immune control such as the human leukocyte antigen (HLA) system. Class I and Class II HLA molecules are essential for peptide presentation which is required for T lymphocyte activation. Single nucleotide polymorphisms within non-coding regions of HLA Class I and Class II genes may influence the expression of these genes by affecting the binding of transcription factors and chromatin modeling molecules. Furthermore, an interplay between genetic and epigenetic factors may also influence HLA expression. Epigenetic factors such as DNA methylation and non-coding RNA, regulate gene expression without changing the DNA sequence. However, genetic variation may promote or allow genes to escape regulation by epigenetic factors, resulting in altered expression. The HLA system is central to most diseases, therefore, understanding the role of genetics and epigenetics on HLA regulation will tremendously impact healthcare. The knowledge gained from these studies may lead to novel and cost-effective diagnostic approaches and therapeutic interventions. This review discusses the role of non-coding variants on HLA regulation. Furthermore, we discuss the interplay between genetic and epigenetic factors on the regulation of HLA by evaluating literature based on polymorphisms within DNA methylation and miRNA regulatory sites within class I and Class II HLA genes. We also provide insight into the importance of the HLA non-coding genome on disease, discuss ethnic-specific differences across the HLA region and provide guidelines for future HLA studies.
非编码基因组内的变异可能会影响参与免疫控制的重要基因的调控和表达，如人类白细胞抗原（HLA）系统。I类和II类HLA分子对于T淋巴细胞激活所需的肽呈递至关重要。HLA I类和II类基因非编码区域内的单核苷酸多态性可能通过影响转录因子和染色质建模分子的结合来影响这些基因的表达。此外，遗传因素和表观遗传因素之间的相互作用也可能影响HLA的表达。DNA甲基化和非编码RNA等表观遗传因素在不改变DNA序列的情况下调节基因表达。然而，遗传变异可能会促进或使基因逃避表观遗传因素的调控，从而导致表达改变。HLA系统在大多数疾病中都起着核心作用，因此，了解遗传学和表观遗传学在HLA调控中的作用将对医疗保健产生巨大影响。从这些研究中获得的知识可能会带来新颖且具有成本效益的诊断方法和治疗干预措施。本综述讨论了非编码变异在HLA调控中的作用。此外，我们通过评估基于I类和II类HLA基因内DNA甲基化和miRNA调控位点多态性的文献，讨论了遗传因素和表观遗传因素在HLA调控中的相互作用。我们还深入探讨了HLA非编码基因组对疾病的重要性，讨论了HLA区域的种族特异性差异，并为未来的HLA研究提供指导。
