CDKN2B methylation is associated with carotid artery calcification in ischemic stroke patients
Shuyu Zhou1, Yumeng Zhang2, Li Wang3
1Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
Background:
Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) near chromosome 9p21 have been associated with both atherosclerosis and artery calcification, but the underlying mechanisms remained largely unknown. Considering that CDKN2A/2B is a frequently reported site for DNA methylation, this study aimed to evaluate whether carotid artery calcification (CarAC) is related to methylation levels of CDKN2A/2B in patients with ischemic stroke.
Methods:
DNA methylation levels of CDKN2A/2B were measured in 322 ischemic stroke patients using peripheral blood leukocytes. Methylation levels of 36 CpG sites around promoter regions of CDKN2A/2B were examined with BiSulfite Amplicon Sequencing. CarAC was quantified with Agatston score based on results of computed tomography angiography. Generalized liner model was performed to explore the association between methylation levels and CarAC.
Results:
Of the 322 analyzed patients, 187 (58.1%) were classified as with and 135 (41.9%) without evident CarAC. The average methylation levels of CDKN2B were higher in patents with CarAC than those without (5.7 vs 5.4, p = 0.001). After adjustment for potential confounders, methylation levels of CDKN2B were positively correlated with cube root transformed calcification scores (β = 0.591 ± 0.172, p = 0.001) in generalized liner model. A positive correlation was also detected between average methylation levels of CDKN2B and cube root transformed calcium volumes (β = 0.533 ± 0.160, p = 0.001).
Conclusions:
DNA methylation of CDKN2B may play a potential role in artery calcification.
Insights
DNA methylation of CDKN2B is linked to artery calcification in ischemic stroke patients. Higher CDKN2B methylation levels correlate with increased carotid artery calcification (CarAC) severity.
Area of Science:
- Cardiovascular Research
- Epigenetics
- Stroke Medicine
Background:
- The Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) locus at chromosome 9p21 is implicated in atherosclerosis and artery calcification.
- Mechanisms linking CDKN2A/2B to vascular calcification, particularly DNA methylation, remain unclear.
- CDKN2A/2B is a known site for DNA methylation, prompting investigation into its role in artery calcification.
Purpose of the Study:
- To investigate the association between DNA methylation levels of CDKN2A/2B and carotid artery calcification (CarAC) in patients with ischemic stroke.
- To determine if epigenetic modifications at the CDKN2A/2B locus contribute to the development or progression of CarAC.
Main Methods:
- DNA methylation levels of CDKN2A/2B were quantified in 322 ischemic stroke patients using peripheral blood leukocytes.
- Bisulfite Amplicon Sequencing analyzed methylation at 36 CpG sites within CDKN2A/2B promoter regions.
- Carotid artery calcification (CarAC) was assessed using Agatston scores from computed tomography angiography.
Main Results:
- Carotid artery calcification (CarAC) was present in 58.1% of the study cohort.
- Patients with CarAC exhibited significantly higher average CDKN2B methylation levels compared to those without (5.7 vs. 5.4, p=0.001).
- Adjusted analyses revealed a positive correlation between CDKN2B methylation and both calcification scores (β=0.591±0.172, p=0.001) and calcium volumes (β=0.533±0.160, p=0.001).
Conclusions:
- DNA methylation of CDKN2B is a potential contributing factor in the pathogenesis of artery calcification.
- These findings suggest an epigenetic mechanism linking CDKN2A/2B to vascular calcification in ischemic stroke patients.
- Further research is warranted to elucidate the precise role of CDKN2B methylation in cardiovascular disease.
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