Methylation of p15INK4b and Expression of ANRIL on Chromosome 9p21 Are Associated with Coronary Artery Disease

Zhuang, Jianhua; Peng, Wenhui; Li, Hailing; Wang, Wei; Wei, Yidong; Li, Weiming; Xu, Yawei

doi:10.1371/journal.pone.0047193

Cited by 80 publications

(55 citation statements)

References 48 publications

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“…One of the major mechanisms to down-regulate expression of a gene is methylation of a cytosine and guanine rich area, called CpGislands, in the promoter region of the gene [9]. A few studies have indicated that DNA promoter methylation of certain genes is responsible for the susceptibility of CHD [10]–[13].…”

Section: Introductionmentioning

confidence: 99%

A Preliminary Study of the Relationship between Promoter Methylation of the ABCG1, GALNT2 and HMGCR Genes and Coronary Heart Disease

Peng

Wang

et al. 2014

PLoS ONE

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AimsTo investigate the association of ABCG1, GALNT2 and HMGCR genes promoter DNA methylation with coronary heart disease (CHD) and explore the interaction between their methylation status and the CHD patients' clinical characteristics in Han Chinese population.Methods and resultsMethylation-specific polymerase chain reaction (MSP) technology was used to examine the role of the aberrant gene promoter methylation in CHD in Han Chinese population. A total of 85 CHD patients and 54 participants without CHD confirmed by angiography were recruited. 82.8% of the participants with ABCG1 gene promoter hypermethylation have CHD, while only 17.4% of the participants without hypermethylation have it. The average age of the participants with GALNT2 gene promoter hypermethylation is 62.10±8.21, while that of the participants without hypermethylation is 57.28±9.87; in the former group, 75.4% of the participants have CHD, compared to only 50% in the latter group. As for the HMGCR gene, the average age of the participants with promoter hypermethylation is 63.24±8.10 and that of the participants without hypermethylation is 57.79±9.55; its promoter hypermethylation is likely to be related to smoking. Our results indicated a significant statistical association of promoter methylation of the ABCG1 gene with increased risk of CHD (OR = 19.966; 95% CI, 7.319–54.468; P *<0.001; P *: adjusted for age, gender, smoking, lipid level, hypertension, and diabetes). Similar results were obtained for that of the GALNT2 gene (OR = 2.978; 95% CI, 1.335–6.646; P * = 0.008), but not of HMGCR gene (OR = 1.388; 95% CI, 0.572–3.371; P * = 0.469).ConclusionsThe present work provides evidence to support the association of promoter DNA methylation status with the risk profile of CHD. Our data indicates that promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. CHD, smoking and aging are likely to be the important factors influencing DNA hypermethylation.

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Section: Introductionmentioning

confidence: 99%

A Preliminary Study of the Relationship between Promoter Methylation of the ABCG1, GALNT2 and HMGCR Genes and Coronary Heart Disease

Peng

Wang

et al. 2014

PLoS ONE

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“…29 Cross-sectionally, hypermethylation of PLA2G7 was associated with coronary heart disease (CHD) among females 30 and hypermethylation of a locus on 9p21, a region of robust genetic associations with CVD, was more prevalent among coronary artery disease cases in a Chinese population. 51 …”

Section: Candidate Gene Methylation Studiesmentioning

confidence: 99%

Clinical applications of epigenetics in cardiovascular disease: the long road ahead

Aslibekyan

Claas

Arnett

2015

Translational Research

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Epigenetic processes, defined as heritable changes in gene expression that occur without changes to the DNA sequence, have emerged as a promising area of cardiovascular disease research. Epigenetic information transcends that of the genotype alone, and provides for an integrated etiologic picture of cardiovascular disease pathogenesis because of the interaction of the epigenome with the environment. Epigenetic biomarkers, which include DNA methylation, histone modifications, and RNA-based mechanisms, are both modifiable and cell-type specific, which makes them not only responsive to the environment, but also an attractive target for drug development. However, the enthusiasm surrounding possible applications of cardiovascular epigenetics currently outpaces available evidence. In this review, we synthesize the evidence linking epigenetic changes with cardiovascular disease, emphasizing the gap between the translational potential and the clinical reality of cardiovascular epigenetics.

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“…Cytokines' haplotypes comprising of CAD-susceptible alleles could significantly affect the disease pathophysiology by up-regulating the inflammatory markers expression. Furthermore, evidence shows that methylation of P15INK4B appears to be involved in the pathogenesis of CAD [33]. This suggests that promoter region methylation is another factor that may influence gene expression.…”

Section: Role Of Cytokines Signaling Pathway In Cadmentioning

confidence: 99%

Clinical Implications of Tumor Necrosis Factor-Alpha, Interleukin-6 and Resistin in Coronary Artery Disease

Javed¹

2014

WJCD

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Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are involved in the progression of coronary artery disease (CAD). The cytokines' levels are associated with the severity of CAD. We have recently reported on the association of resistin, a relatively novel cytokine with the pathogenesis of cardiovascular disease (CVD). Although the inflammatory cytokines' impact on atherosclerosis is widely accepted, yet some controversy exists regarding the involvement of these factors in atherogenesis. The current review highlights the potential association of TNF-alpha, IL-6 and resistin SNPs (single nucleotide polymorphisms) with CAD. Molecular genetics data along with the intracellular signaling cascade mechanisms may have important clinical implications in the treatment of CAD.

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Methylation of p15INK4b and Expression of ANRIL on Chromosome 9p21 Are Associated with Coronary Artery Disease

Cited by 80 publications

References 48 publications

A Preliminary Study of the Relationship between Promoter Methylation of the ABCG1, GALNT2 and HMGCR Genes and Coronary Heart Disease

A Preliminary Study of the Relationship between Promoter Methylation of the ABCG1, GALNT2 and HMGCR Genes and Coronary Heart Disease

Clinical applications of epigenetics in cardiovascular disease: the long road ahead

Clinical Implications of Tumor Necrosis Factor-Alpha, Interleukin-6 and Resistin in Coronary Artery Disease

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