lncRNA involvement in immune-related diseases - from SNP association to implication in pathogenesis and therapeutic potential

Development of new high throughput array-based techniques and, more recently, next-generation sequencing (NGS) technologies have revolutionized our capability to accurately characterize single nucleotide polymorphisms (SNPs) throughout the genome. These advances have facilitated large-scale genome-wide association studies (GWAS), which have served as fundamental elements in establishing links between SNPs and the susceptibility to several complex diseases, including those related to the immune system. Nevertheless, the molecular mechanisms underlying the development of most of these disorders are still poorly defined. Decoding the functionality of SNPs becomes increasingly challenging due to the predominant presence of these risk variants in non-coding regions of the genome. Among them, long non-coding RNAs (lncRNAs) are enriched in disease-associated SNPs. lncRNAs are involved in governing the control of gene expression both during transcription and at the post-transcriptional level. The existence of SNPs within the sequences of lncRNAs has the potential to alter their expression, structure, or function. This, in turn, can influence their regulatory roles and consequently contribute to the onset or progression of various diseases. In this review, we describe the implication of SNPs located in lncRNAs in the development of different immune-related diseases and highlight the potential of these molecules in the development of emerging RNA-based therapies.