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.
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.
BackgroundThe low rates of hypertension treatment and control, partly due to its unawareness, are the main causes of the high stroke incidence in China. The purpose of this study was to evaluate hypertension unawareness amongst patients with first-ever stroke and to detect factors associated with its unawareness.MethodsWe selected those diagnosed with hypertension from patients with first-ever stroke registered in the Nanjing Stroke Registry Program between 2004 and 2014. These hypertensives were divided as being aware or unaware of their hypertension by using a brief questionnaire conducted shortly after the stroke. Multivariate logistic regression analysis was performed to identify potential factors associated with hypertension unawareness.ResultsOf the 5309 patients with first-ever stroke, 3732 (70.3 %) were diagnosed with hypertension. Among which, 593 (15.9 %) were unaware of their hypertension at the time of stroke onset. Lower-level of education (primary school or illiteracy) and smoking were associated positively with hypertension unawareness; while advanced age, overweight, diabetes mellitus, heart diseases and family history of stroke were associated negatively with hypertension unawareness. Annual data analyzed indicated that the rate of hypertension awareness increased during the past 11 years (r = 0.613, P = 0.045 for trends).ConclusionsA substantial proportion (15.9 %) of Chinese patients with hypertension had not been aware of this covert risk until an overt stroke occurred. Hypertension unawareness was associated with lower educational levels and smoking, which address the importance of health education especially in these individuals.
MicroRNAs are a recently discovered class of small noncoding RNA, which play key roles in every aspect of brain function, including neural development and neurogenesis. Since abnormal expression and function of microRNAs has been observed in ischemic stroke, we evaluated whether genetic variations in microRNAs can influence the clinical behavior of ischemic stroke. Common functional microRNA SNPs (i.e., miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, miR-499 rs3746444, miR-605 rs2043556, and miR-618 rs2682818) were genotyped in 914 patients with ischemic stroke. MicroRNAs variants were not associated with age of ischemic stroke onset (P > 0.05). However, we found that miR-618 rs2682818 GT/TT genotypes were significantly associated with an increased risk of ischemic stroke recurrence, compared with the GG genotype (hazard ratio [HR] = 1.72; 95 % confidential interval [CI], 1.08 to 2.74; log-rank P = 0.006), and this effect was more pronounced among subjects with small-vessel disease (HR = 2.60; 95 % CI, 1.11 to 6.08; log-rank P = 0.007). Moreover, the variant genotypes (GT/TT) of rs2682818 were an independent prognostic factor for ischemic stroke in the multivariate Cox regression model. Our findings suggest that miR-618 SNP rs2682818 may play an important role in the recurrence of ischemic stroke.
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