title: CDKN2B methylation is associated with carotid artery calcification in ischemic stroke patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  DNA methylation of CDKN2B may play a potential role in artery calcification.
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Gerontology, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 21008, China.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Biyang
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, 21002, China.
authors.forename: Keting
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, 21002, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China. cjr.luguangming@vip.163.com.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China. gelinxu@nju.edu.cn.
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D002114:Calcinosis / Q000150:complications / Q000235:genetics*; D002339:Carotid Arteries / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000235:genetics*
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15
keywords: CDKN2A/2B; Carotid artery calcification; DNA methylation; Ischemic stroke