From molecular mechanisms to clinical implications of clock genes in ischemic stroke: A scoping review

Sleep and circadian rhythms are closely linked to ischemic stroke (IS) risk and outcomes; however, the molecular mechanisms underlying this relationship remain incompletely understood. This scoping review focuses on the roles of clock genes in IS, integrating evidence from animal and human studies.

This scoping review followed the PRISMA guidelines. We searched eight English and Chinese databases (up to May 10, 2026) for human and animal studies examining the role of circadian clock genes in ischemic stroke onset, progression, or prognosis. Data related to the study design, specific clock genes, and key outcomes were extracted. Primary studies and review articles were synthesized separately to minimize aggregation bias. This scoping review followed the PRISMA-ScR guidelines.

19 studies were included: 9 animal model studies, 2 human case-control studies, and 8 review articles. Primary evidence suggests that clock genes may influence stroke susceptibility and severity. Notably, the PER1 rs2253820 variant was associated with increased IS risk. Ischemic stroke might also alter the expression of PER1 and CRY1, leading to imbalances in sleep-wake architecture. Circadian variations in stroke severity may be related to the expression of clock genes. This relationship was also influenced by age and gender.

Clock genes may influence the brain's response to ischemic stress. Large-scale human studies are still needed to confirm the two-way relationship between stroke and clock genes before these gene polymorphisms can be used for prediction or treatment.