A Common Functional Variant at the Enhancer of the Rheumatoid Arthritis Risk Gene ORMDL3 Regulates its Expression Through Allele-Specific JunD Binding.

ABSTRACT: Genome-wide association studies (GWASs) have identified over 100 loci associated with rheumatoid arthritis (RA); however, the functionally affected genes and the underlying molecular mechanisms contributing to these associations are often unknown. In this study, we conducted an integrative genomic analysis incorporating multiple "omics" data and identified a functional regulatory DNA variant, rs56199421, and a plausible mechanism by which it regulates the expression of a putative RA risk gene, ORMDL Sphingolipid Biosynthesis Regulator 3 (ORMDL3). The T allele of rs56199421, located in the enhancer region of ORMDL3, exhibited stronger direct binding ability than the other C allele of rs56199421 did in vitro with the transcription factor JunD and demonstrated higher tran

SUBMITTER: Ye W 

PROVIDER: S-EPMC10593690 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature