<i>KLF2</i> enhancer variant rs4808485 increases lupus risk by modulating inflammasome machinery and cellular homoeostasis.

ABSTRACT:

Objective

A recent genome-wide association study linked KLF2 as a novel Asian-specific locus for systemic lupus erythematosus (SLE) susceptibility. However, the underlying causal functional variant(s), cognate target gene(s) and genetic mechanisms associated with SLE risk are unknown.

Methods

We used bioinformatics to prioritise likely functional variants and validated the best candidate with diverse experimental techniques, including genome editing. Gene expression was compared between healthy controls (HCs) and patients with SLE with or without lupus nephritis (LN+, LN-).

Results

Through bioinformatics and expression quantitative trait locus analyses, we prioritised rs4808485 in active chromatin, predicted to modulate KLF2 expression. Luciferase reporter assays and

SUBMITTER: Singh MK 

PROVIDER: S-EPMC11168881 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature