Asthma is a widespread complicated disease with evident genetic predispositions, and prior genome-wide association studies suggest that the IL13 (interleukin 13) gene variant rs1295686 is significantly linked to asthma. According to the 1000 Genomes Project’s data, four more SNPs in Caucasians were in almost full linkage disequilibrium with rs1295686. However, the causal SNPs and the mechanism that underpins them were unknown. Researchers used Functional genomics techniques to examine the functionalities of these SNPs to investigate this issue. According to dual-luciferase tests, the functional SNP was not rs1295686 but a haplotype that includes rs1295685, rs848, and rs847.
According to chromosomal conformation capture, the enhancer comprising the three functional SNPs interacts with the promoter of TH2LCRR (T helper type 2 locus control region associated RNA), a recently discovered long non-coding RNA. RNA-seq data analysis revealed that TH2LCRR expression was considerably higher in asthma patients and was genotype-dependent, implying that TH2LCRR was a novel asthma susceptibility gene. These SNPs confer asthma risk by influencing TH2LCRR expression. The associated transcription factors that bind in the region surrounding these three SNPs were identified using chromatin immunoprecipitation, and their interactions were examined using functional genomics techniques. This research discovered a novel mechanism by which genetic differences at this locus may affect asthma susceptibility.
Reference:www.atsjournals.org/doi/abs/10.1165/rcmb.2020-0481OC
