Related Experiment Video
Updated: Dec 21, 2025
Author Spotlight: Innovative Techniques for ROS Detection and Implications for Platelet Research
Published on: March 29, 2024
NADPH Oxidase Gene Polymorphism is Associated with Mortality and Cardiovascular Events in 7-Year Follow-Up
Milena Racis1, Wojciech Sobiczewski1, Anna Stanisławska-Sachadyn2,3
1First Department of Cardiology, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland.
Insights
The CYBA gene
Area of Science:
- Genetics and Cardiovascular Disease
- Molecular Biology and Pathophysiology
- Biochemistry and Redox Signaling
Background:
- The CYBA gene encodes a subunit of NADPH oxidase, crucial for cellular and vascular redox balance.
- NADPH oxidase activity is implicated in the pathophysiology of coronary artery disease (CAD).
- CYBA gene polymorphisms may influence CAD progression and clinical outcomes.
Purpose of the Study:
- To investigate the association between CYBA gene polymorphisms and the course of coronary artery disease (CAD).
- To evaluate the impact of specific CYBA polymorphisms on mortality, major adverse cardiovascular events (MACE), and revascularization procedures.
- To explore the potential role of CYBA variants in atherosclerotic plaque stability and disease progression.
Main Methods:
- A 7-year follow-up study of 1197 patients with coronary atherosclerosis.
- Genotyping of three CYBA polymorphisms: c.214C>T (rs4673), c.-932G>A (rs9932581), and c.*24G>A (1049255).
- Statistical analysis to assess the association between CYBA genotypes and clinical endpoints including death, MACE, and PCI/CABG.
Main Results:
- The CYBA c.214C>T polymorphism was significantly associated with death and PCI/CABG.
- The CYBA c.214TT genotype showed a lower risk of death (9.5% vs. 21%) compared to the C allele.
- The CYBA c.214TT genotype was linked to a higher risk of elective PCI/CABG (69.3% vs. 51.7%) compared to the C allele.
Conclusions:
- The CYBA c.214TT genotype may confer protection against death in patients with coronary atherosclerosis (OR=0.47).
- This genotype also appears to be a risk factor for undergoing elective PCI/CABG (OR=2.36).
- The CYBA c.214TT genotype might promote atherosclerotic plaque stability, shifting CAD towards a chronic course and reducing fatal events.
Abstract:
The CYBA gene encodes the regulatory subunit of NADPH oxidase, which maintains the redox state within cells and in the blood vessels. That led us to investigate the course of coronary artery disease (CAD) with regards to CYBA polymorphisms. Thus, we recruited 1197 subjects with coronary atherosclerosis and observed them during 7-year follow-up. Three CYBA polymorphisms: c.214C>T (rs4673), c.-932G>A (rs9932581), and c.*24G>A (1049255) were studied for an association with death, major adverse cardiovascular events (MACE) and an elective percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG). We found an association between the CYBA c.214C>T polymorphism and two end points: death and PCI/CABG. CYBA c.214TT genotype was associated with a lower risk of death than C allele (9.5% vs. 21%, p < 0.05) and a higher risk of PCI/CABG than C allele (69.3% vs. 51.7%, p < 0.01). This suggests that the CYBA c.214TT genotype may be a protective factor against death OR = 0.47 (95%CI 0.28-0.82; p < 0.01), while also being a risk factor for an elective PCI/CABG OR = 2.36 (95%CI 1.15-4.82; p < 0.05). Thus, we hypothesize that among patients with coronary atherosclerosis, the CYBA c.214TT genotype contributes to atherosclerotic plaque stability by altering the course of CAD towards chronic coronary syndrome, thereby lowering the incidence of fatal CAD-related events.
