Shuyu Zhou1, Biyang Cai1, Zhizhong Zhang1, Yumeng Zhang2, Li Wang3, Keting Liu4, Hao Zhang1, Lingli Sun1, Huan Cai4, Guangming Lu3, Xinfeng Liu1, Gelin Xu1. 1. Department of Neurology, Jinling Hospital, Medical School of Nanjing University. 2. Department of Gerontology, Nanjing Drum Tower Hospital, Medical School of Nanjing University. 3. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University. 4. Department of Neurology, Jinling Hospital, Southern Medical University.
Abstract
AIM: 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). CONCLUSION: 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.
AIM: 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). CONCLUSION: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.
Entities:
Keywords:
Aortic arch calcification; CDKN2A/2B; DNA methylation; Ischemic stroke
Authors: Terence M Doherty; Kamlesh Asotra; Lorraine A Fitzpatrick; Jian-Hua Qiao; Douglas J Wilkin; Robert C Detrano; Colin R Dunstan; Prediman K Shah; Tripathi B Rajavashisth Journal: Proc Natl Acad Sci U S A Date: 2003-09-19 Impact factor: 11.205
Authors: Jessica van Setten; Ivana Isgum; Joanna Smolonska; Stephan Ripke; Pim A de Jong; Matthijs Oudkerk; Harry de Koning; Jan-Willem J Lammers; Pieter Zanen; Harry J M Groen; H Marike Boezen; Dirkje S Postma; Cisca Wijmenga; Max A Viergever; Willem P Th M Mali; Paul I W de Bakker Journal: Atherosclerosis Date: 2013-03-13 Impact factor: 5.162