Convergent Evidence SupportsTH2LCRRas a Novel Asthma Susceptibility Gene

• DOI: 10.1165/rcmb.2020-0481oc
• Publication Date: 2021-12-01T19:54:53Z
• Authors: Yi-Kun Li; Xin-Xin Zhang; Yuan Yang; Jing Gao; Qiang Shi; Shao-Dong Liu; Wei-Ping Fu; Chang Sun
• Keywords: Linkage Disequilibrium; Genetic Association; Genome-wide Association Study; SNP; Functional Genomics

Asthma is a common, complex disease with apparent genetic predispositions, and previous genome-wide association studies suggest that rs1295686 within the IL13 (IL-13) gene significantly associated asthma. Analysis of data provided by 1,000 Genomes Project indicated an additional four SNPs in nearly complete linkage disequilibrium White people. However, causal mechanism remain unclear. To investigate this issue, functional genomics approaches were utilized to analyze functions these SNPs. Dual-luciferase assays SNP not but haplotype consisting three other SNPs: rs1295685, rs848, rs847. Through chromosome conformation capture, it was found enhancer containing interacts promoter TH2LCRR (T helper type 2 locus control region RNA), recently identified long noncoding RNA. RNA-seq analysis expression increased patients asthma dependent on genotype at locus, indicating novel susceptibility for confer risk regulating expression. By chromatin immunoprecipitation, related transcription factors bind surrounding identified, their interactions investigated approaches. Our effort through which variations could influence susceptibility.