CDKN2B methylation is associated with carotid artery calcification in ischemic stroke patients

Abstract

BackgroundCyclin-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.MethodsDNA 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.ResultsOf 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).ConclusionsDNA methylation of CDKN2B may play a potential role in artery calcification.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1093-4) contains supplementary material, which is available to authorized users.

Retracted Article: LncRNA OIP5-AS1 contributes to ox-LDL-induced inflammation and oxidative stress through regulating the miR-128-3p/CDKN2A axis in macrophages

“…Cyclin-dependent kinase inhibitor 2A (CDKN2A) has been identied as a cell cycle regulator and is related to the modulation of platelets. 18,19 The location of CDKN2A was found to be close to chromosome 9p21 (chr9p21). Motterle et al indicated that chr9p21 variation affected the level of CDKN2A through regulating lncRNA ANRIL expression, which modulates the proliferation of vascular smooth muscle cells and enhances AS.…”

“…Motterle et al indicated that chr9p21 variation affected the level of CDKN2A through regulating lncRNA ANRIL expression, which modulates the proliferation of vascular smooth muscle cells and enhances AS. 18,20 Therefore, CDKN2A is clearly related to the development of AS. However, whether CDKN2A mediates ox-LDL-induced cell progression in AS is unknown.…”

Advancing stroke genomic research in the age of Trans-Omics big data science: Emerging priorities and opportunities

“…71 In ischemic stroke patients, CDKN2B methylation in peripheral blood leukocytes was found to be associated with carotid artery calcification. 72 . Epigenomic study discovered that DNA methylation level for TRAF3 gene is associated with vascular recurrence in ischemic stroke patients treated with clopidogrel.…”

Involvement of methylation-associated silencing of formin 2 in colorectal carcinogenesis

“…MethylTarget ™ assays (targeted bisulfite sequencing) developed by Genesky BioTech (Shanghai, China) were carried out as previously described[ 9 , 10 ]. Briefly, CpG islands adjacent to the promoter region of the FMN2 gene were analyzed, and based on these CpG islands, four CpG regions from CpG islands in FMN2 were sequenced (the details, including the relative distance from the transcriptional start site, amplification primers, and product size, of these CpG regions can be found in Tables 2 and 3 ).…”