GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin...

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Veröffentlicht in:Pharmacological research 2025-02, Vol.212, p.107575, Article 107575
Hauptverfasser: Magavern, Emma F., Deshmukh, Harshal, Asselin, Geraldine, Theusch, Elizabeth, Trompet, Stella, Li, Xiaohui, Noordam, Raymond, Chen, Y.-D. Ida, Seeman, Teresa E., Taylor, Kent D., Post, Wendy S., Tardif, Jean-Claude, Paul, Dirk S., Benjamin, Emelia J., Heard-Costa, Nancy L., Vasan, Ramachandran S., Rotter, Jerome I., Krauss, Ronald M., Jukema, J.Wouter, Ridker, Paul M., Munroe, Patricia B., Caulfield, Mark J., Chasman, Daniel I., Dubé, Marie-Pierre, Hitman, Graham A., Warren, Helen R.
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Sprache:eng
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Zusammenfassung:Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P 
ISSN:1043-6618
1096-1186
1096-1186
DOI:10.1016/j.phrs.2024.107575