Zhou Shuyu, Zhang Yumeng, Wang Li, Zhang Zhizhong, Cai Biyang, Liu Keting, Zhang Hao, Dai Minhui, Sun Lingli, Xu Xiaomeng, Cai Huan, Liu Xinfeng, Lu Guangming, Xu Gelin
Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 21002, China.
Department of Gerontology, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 21008, China.
J Transl Med. 2016 Dec 1;14(1):333. doi: 10.1186/s12967-016-1093-4.
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.
9号染色体短臂21区附近的细胞周期蛋白依赖性激酶抑制剂2A/2B（CDKN2A/2B）与动脉粥样硬化和动脉钙化均有关联，但其潜在机制仍不清楚。鉴于CDKN2A/2B是一个经常报道的DNA甲基化位点，本研究旨在评估缺血性脑卒中患者的颈动脉钙化（CarAC）是否与CDKN2A/2B的甲基化水平相关。
采用外周血白细胞检测322例缺血性脑卒中患者CDKN2A/2B的DNA甲基化水平。通过亚硫酸氢盐扩增子测序检测CDKN2A/2B启动子区域周围36个CpG位点的甲基化水平。根据计算机断层血管造影结果，用阿加斯顿积分对CarAC进行量化。采用广义线性模型探讨甲基化水平与CarAC之间的关联。
在322例分析患者中，187例（58.1%）被归类为有明显CarAC，135例（41.9%）无明显CarAC。有CarAC的患者中CDKN2B的平均甲基化水平高于无CarAC的患者（5.7对5.4，p = 0.001）。在对潜在混杂因素进行校正后，广义线性模型中CDKN2B的甲基化水平与立方根转换后的钙化积分呈正相关（β = 0.591±0.172，p = 0.001）。CDKN2B的平均甲基化水平与立方根转换后的钙体积之间也检测到正相关（β = 0.533±0.160，p = 0.001）。
CDKN2B的DNA甲基化可能在动脉钙化中起潜在作用。
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