A Non-Coding Variant in SLC15A4 Modulates Enhancer Activity and Lysosomal Deacidification Linked to Lupus Susceptibility.

ABSTRACT: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic basis. Despite the identification of several single nucleotide polymorphisms (SNPs) near the SLC15A4 gene that are significantly associated with SLE across multiple populations, specific causal SNP(s) and molecular mechanisms responsible for disease susceptibility are unknown. To address this gap, we employed bioinformatics, expression quantitative trait loci (eQTLs), and 3D chromatin interaction analysis to nominate a likely functional variant, rs35907548, in an active intronic enhancer of SLC15A4. Through luciferase reporter assays followed by chromatin immunoprecipitation (ChIP)-qPCR, we observed significant allele-specific enhancer effects of rs35907548 in diverse cell lines. The rs35

SUBMITTER: Singh MK 

PROVIDER: S-EPMC10843804 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature