Lupus & antiphospholipid syndrome
Integrative Functional Genomics Identifies Systemic Lupus Erythematosus Causal Genetic Variant in the IRF5 Risk Locus
Authors' conclusion
These results demonstrate that the rs4728142-A allele increases the SLE risk by affecting ZBTB3 binding, chromatin status, and regulating IRF5 expression, establishing a biologic link between genetic variation and lupus pathogenesis.
Study context
- Population
- Systemic lupus erythematosus (SLE) risk variants in the IRF5 locus; monocytes from SLE patients
- Outcome
- Regulatory function and mechanisms of SLE IRF5 enhancer risk variants
Methodological detailsintegrative functional genomics, CRISPR-mediated deletion, activation and interference, allele-specific ChIP-qPCR and FAIRE-qPCR
- Integrative functional genomics
- CRISPR-mediated deletion, activation and interference
- Allele-specific ChIP-qPCR and FAIRE-qPCR
Main finding
As reported in the abstract
- SLE risk SNP rs4728142 located in an enhancer region; risk allele rs4728142-A closely associated with increased IRF5 expression
- rs4728142-containing region acts as an enhancer regulating IRF5 expression
- rs4728142 affected the binding affinity of the transcription factor ZBTB3
- In monocytes from SLE patients, clustered regularly interspaced short palindromic repeat interference (CRISPRi) of this enhancer attenuated production of disease-associated cytokines
Original publication
Integrative Functional Genomics Identifies Systemic Lupus Erythematosus Causal Genetic Variant in the IRF5 Risk Locus. Arthritis Rheumatol. Published 8 February 2023. doi:10.
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