title: CDKN2B Methylation and Aortic Arch Calcification in Patients with Ischemic Stroke.
abstract: OBJECTIVE
  CDKN2A/2B near chromosome 9p21 has been proposed as a potential genetic etiology for both atherosclerosis and arterial calcification. DNA methylation, which can change the expression of CDKN2A/2B, may be an underlying mechanism for this association. This study aimed to evaluate whether CDKN2A/2B methylation is related to aortic arch calcification (AAC) in patients with ischemic stroke.
  
  
  METHODS
  DNA methylation levels of CDKN2A/2B was measured using venous blood samples in 322 patients with ischemic stroke. A total of 36 CpG sites around promoter regions of CDKN2A/2B were examined. AAC was quantified with Agatston score based on results of computed tomography angiography.
  
  
  RESULTS
  There were 248 (77.0%) patients with and 74 (23.0%) patients without evident AAC. Compared with patients without AAC, patients with AAC had higher methylation levels of CDKN2B (5.72 vs 4.94, P＜0.001). Using a generalized linear model, positive correlation between methylation levels and log-transformed calcification scores was detected at CDKN2B (β=0.275±0.116, P= 0.018).
  
  
  CONCLUSIONS
  Patients with higher levels of DNA methylation of CDKN2B may bear increased risk for AAC. Further studies to reveal the underlying mechanisms of this association are warranted for establishing a cause-effect relationship.
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Shuyu
authors: S
authors: Zhou
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Biyang
authors: B
authors: Cai
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Zhizhong
authors: Z
authors: Zhang
authors: Department of Gerontology, Nanjing Drum Tower Hospital, Medical School of Nanjing University.
authors: Yumeng
authors: Y
authors: Zhang
authors: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University.
authors: Li
authors: L
authors: Wang
authors: Department of Neurology, Jinling Hospital, Southern Medical University.
authors: Keting
authors: K
authors: Liu
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Hao
authors: H
authors: Zhang
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Lingli
authors: L
authors: Sun
authors: Department of Neurology, Jinling Hospital, Southern Medical University.
authors: Huan
authors: H
authors: Cai
authors: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University.
authors: Guangming
authors: G
authors: Lu
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Xinfeng
authors: X
authors: Liu
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University.
authors: Gelin
authors: G
authors: Xu
mesh_terms: D000368:Aged; D000428:Alcohol Drinking; D001013:Aorta, Thoracic / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics; D002114:Calcinosis / Q000378:metabolism*; D002681:China; D002875:Chromosomes / Q000648:ultrastructure; D000072226:Computed Tomography Angiography; D018899:CpG Islands; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism*; D019175:DNA Methylation; D050171:Dyslipidemias / Q000150:complications; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012907:Smoking; D020521:Stroke / Q000235:genetics / Q000378:metabolism*; D061205:Vascular Calcification / Q000235:genetics*
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15
keywords: Aortic arch calcification; CDKN2A/2B; DNA methylation; Ischemic stroke