2025-08-26 ミュンヘン大学(LMU)
<関連情報>
- https://www.lmu.de/en/newsroom/news-overview/news/human-genetics-gene-variant-protects-against-cardiovascular-diseases.html
- https://www.nature.com/articles/s44161-025-00700-7
IL-6遺伝子の撹乱によるIL-6阻害を模倣した状態は、心代謝リスクの低下と関連している IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk
Lanyue Zhang,Murad Omarov,Lingling Xu,Emil deGoma,Pradeep Natarajan & Marios K. Georgakis
Nature Cardiovascular Research Published:26 August 2025
DOI:https://doi.org/10.1038/s44161-025-00700-7
Abstract
Human genetics supports a causal involvement of IL-6 signaling in atherosclerotic cardiovascular disease, prompting the clinical development of anti-IL-6 therapies. Genetic evidence has historically focused on IL6R missense variants, but emerging cardiovascular treatments target IL-6, not its receptor, questioning the translatability of genetic findings. Here we develop a genetic instrument for IL-6 signaling downregulation comprising IL6 locus variants that mimic the effects of the anti-IL-6 antibody ziltivekimab and use it to predict the effects of IL-6 inhibition on cardiometabolic and safety endpoints. Similar to IL6R, we found that genetically downregulated IL-6 signaling via IL6 perturbation is associated with lower lifetime risks of coronary artery disease, peripheral artery disease and ischemic atherosclerotic stroke in individuals of European and East Asian ancestry. Unlike IL6R missense variants linked to bacterial infections, the IL6 instrument was associated with lower risk of pneumonia hospitalization. Our data suggest that IL-6 inhibition can reduce cardiovascular risk without major unexpected safety concerns.
