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Variants at the Interleukin 1 Gene Locus and Pericarditis
Rosa B Thorolfsdottir1, Andrea B Jonsdottir1, Gardar Sveinbjornsson1
1deCODE genetics, Amgen, Reykjavik, Iceland.
JAMA Cardiology
|December 27, 2023
Summary
This study identified two genetic variants linked to interleukin 1 (IL1) in pericarditis patients. These findings may lead to personalized therapies targeting IL1 for treating pericarditis.
Area of Science:
- Genetics
- Immunology
- Cardiology
Background:
- Recurrent pericarditis presents a significant treatment challenge.
- Interleukin 1 (IL1) inhibitors show promise for pericarditis, but underlying biological mechanisms require further elucidation.
- Understanding immune system contributions to pericarditis pathogenesis is incomplete.
Purpose of the Study:
- To investigate the genetic underpinnings of pericarditis using human genomics, transcriptomics, and proteomics.
- To identify genetic variants associated with pericarditis and its subtypes.
- To explore the functional mechanisms linking genetic variants to IL1 production.
Main Methods:
- A meta-analysis of genome-wide association studies (GWAS) involving pericarditis cases from five countries.
- Examination of associations between identified variants and pericarditis subtypes, gene expression (cis-eQTL), plasma protein levels (pQTL), and DNA methylation (ASM-QTL).
- Utilized large-scale genetic data from Iceland, Denmark, the UK, the US, and Finland.
Main Results:
- Identified two independent common intergenic variants at the interleukin 1 (IL1) locus (chromosome 2q14) associated with pericarditis.
- The lead variant, rs12992780, showed a stronger association with acute pericarditis than recurrent pericarditis.
- The variant rs7575402 was linked to DNA methylation patterns affecting transcription factors crucial for IL1 regulation (SPI1, STAT1, STAT3, CEBPB).
Conclusions:
- Established a significant association between pericarditis and specific sequence variants within the interleukin 1 (IL1) gene locus.
- These genetic findings offer a basis for developing targeted, personalized therapies for pericarditis using IL1-blocking agents.
- Provides biological rationale for IL1-targeted treatments in pericarditis management.
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