<i>GCK</i>Gene-Body Hypomethylation Is Associated with the Risk of Coronary Heart Disease

Xu, Limin; Zheng, Dawei; Wang, Lingyan; Jiang, Danjie; Li, Haibo; Liu, Xu; Liao, Qi; Zhang, Lína; Li, Panpan; Shi, Xinbao; Wang, Zhaoyang; L, Sun; Zhou, Qingyun; Li, Ni; Huang, Yi; Le, Yanping; Ye, Meng; Shao, Guofeng; Duan, Shiwei

doi:10.1155/2014/151723

Cited by 32 publications

(36 citation statements)

References 45 publications

(59 reference statements)

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“…This observation indicated that EH was affected by genetic and environmental factors, including DNA methylation status and age. Age was previously revealed to be positively correlated with GCK methylation levels (23), however the present study failed to demonstrate this association. No association between age and CpG1-3 or CpG4 methylation was observed (data not shown).…”

Section: Discussioncontrasting

confidence: 96%

“…Hypermethylation of gene-bodies frequently indicates higher levels of gene expression in human tissues and cell types (8,31). Aberrant methylation of the gene body was observed to contribute to the risk of heart failure (32) and coronary heart disease (23). DNA methylation of gene bodies has major significance in the regulation of gene expression (33).…”

Section: Discussionmentioning

confidence: 99%

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Aberrant methylation of the GCK gene body is associated with the risk of essential hypertension

Fan

Wang²,

Zhong

et al. 2015

Molecular Medicine Reports

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Abstract. Essential hypertension (EH) is commonlyaccompanied by a dysfunction of glucose metabolism. Glucokinase (GCK) is a key enzyme involved in glucose metabolism. The aim of the present study was to investigate whether GCK gene-body methylation contributed to the risk of EH. A total of 47 patients with EH and 47 age-matched controls were recruited for methylation research in the current study. GCK gene-body methylation was measured using bisulphite pyrosequencing technology. DNA methylation levels were closely correlated among CpG1, CpG2 and CpG3 (r>0.70; P<0.001), in contrast with a weaker correlation between CpG4 and the preceding three CpGs (r<0.3 or r=1; P>0.05). Significantly lower CpG1-3 methylation (cases vs. controls, 49.13±5.72 vs. 53.49±7.53%; adjusted P= 0.006) and significantly higher CpG4 methylation (cases vs. controls, 46.34±6.48 vs. 34.74±12.73%; adjusted P=0.002) were observed in patients with EH. The present study indicated that aberrant methylation of the GCK gene body was significantly associated with the risk of EH in the population assessed. The discrepancies between CpG1-3 and CpG4 methylation may suggest distinct roles for each of them in the determination of the risk of EH.

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Section: Discussioncontrasting

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Aberrant methylation of the GCK gene body is associated with the risk of essential hypertension

Fan

Wang²,

Zhong

et al. 2015

Molecular Medicine Reports

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“…Genomic DNA was isolated from tumor samples and then quantified as previously described (11,17). TGFB2 and BCL2L11 methylation levels were measured using bisulfite pyrosequencing technology.…”

Section: Tissuementioning

confidence: 99%

“…DNA conversion was performed using reagents provided in the Zymo EZ DNA Methylation-Gold kit (Zymo Research, Orange, CA, USA). The pyrosequencing procedures were performed as described previously (11,17). The primer sequences of TGFB2 were 5'-GAGTAATTTTAAGTTGGGGAGAAGTTAGT-3' for the forward primer, 5'-Biotin-ACT CCA AAC CCC AAC CCA ACCA-3' for the reverse primer, and 5'-CCA ACC CAA CCA CAA-3' for the sequencing primer.…”

Section: Tissuementioning

confidence: 99%

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TGFB2 and BCL2L11 methylation in male laryngeal cancer patients

Shen

Chen

et al. 2016

Oncology Letters

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Abstract. DNA methylation is a major regulatory mechanism of gene expression. The aim of the present study was to test the association of transforming growth factor β2 (TGFB2) and B cell lymphoma 2-like 11 (BCL2L11) gene methylation with the risk of laryngeal squamous cell carcinoma (LSCC). Using bisulfite pyrosequencing technology, DNA methylation levels of TGFB2 promoter and BCL2L11 gene-body CpG cytosines were measured in 90 LSCC tissues and 90 adjacent normal tissues. Analysis of variance and paired sample t-test were used to determine the association of gene methylation and the risk of LSCC. Our results revealed that there were no differences in TGFB2 and BCL2L11 methylation levels between the LSCC tissues and the paired normal tissues (P>0.05). Further breakdown analyses demonstrated that the association results of the two gene methylation levels and LSCC remained unchanged with the age, smoking history, histological differentiation or clinical stage of the LSCC patients (all adjusted P>0.05). In conclusion, there is no association of TGFB2 promoter and BCL2L11 gene-body methylation with the risk of LSCC in males. IntroductionLaryngeal squamous cell carcinoma (LSCC) is the second most common head and neck cancer in the world (1). The incidence of LSCC in China has exhibited an increasing trend in the young population (2,3). LSCC is a complex disease, and it is hypothesized that both genetic and environmental factors play a role in it (4). Epigenetic modifications, including DNA methylation, are known as the bridging factors of genetics and the environment (5). However, the role of epigenetic modifications in the pathogenesis and progression of LSCC remains to be explained.DNA methylation of CpG islands (CGIs) is a significant regulatory mechanism of gene expression (6). Epigenetic silencing of tumor suppressor genes by promoter hyper methylation is considered to be a significant event in the progression of cancers including leukemia (7), lung cancer (8) and prostate cancer (9). Gene-body methylation levels are also demonstrated to be correlated with gene expression (10,11).TGFB2 is a member of the transforming growth factor β (TGFB) family, which encodes multifunctional peptides in the regulation of cell proliferation, differentiation, adhesion and migration (12). TGFB is able to inhibit tumor growth at the early stages and promote tumor growth at the late stages of disease (13). A previous study has demonstrated that increased TGFB2 promoter methylation level is associated with prostate cancer progression (14). BCL2L11 encodes a member of the BCL-2 (B cell lymphoma 2) protein family, which acts as an apoptotic activator that is involved in a wide variety of cellular activities (15). BCL2L11 methylation has been noted to be associated with the risk of hematological and epithelial cancers (16).In the current study, the methylation levels of TGFB2 and BCL2L11 were investigated in male laryngeal cancer patients to determine whether these epigenetic markers are associated with LSCC risk. Materials and methods

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Association ofGCKgene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients

Zheng

et al. 2019

Clinical Laboratory Analysis

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Backgrounds Clopidogrel resistance (CR), which was manifested as the failure of platelet inhibition in clopidogrel treatment, was likely to lead to cardiovascular events. Our study was aimed to explore the contribution of DNA methylation in glucokinase (GCK) to the CR risk. Methods Among 36 CR and 36 non‐CR acute coronary syndrome (ACS) patients, the platelet functions were evaluated by VerifyNow P2Y12 assay (turbidimetric‐based optical detection) and DNA methylation levels on two fragments of the CGI from the GCK were investigated through bisulfite pyrosequencing methods. In addition, the GCK mRNA expression was analyzed via quantitative real‐time PCR. Lastly, the logistic regression was employed to test the interaction between GCK methylation and nongenetic variables in CR patients. Results Subunit analysis showed that in male patients without DM but suffering from dyslipidemia, the increased methylation of cg18492943 indicated a risk of poor clopidogrel response (male, NCR vs CR(%): 84.86 ± 6.29 vs 88.16 ± 4.32, P = .032; without DM, NCR vs CR (%): 84.66 ± 6.18 vs 88.16 ± 4.17, P = .029; and dyslipidemia, NCR vs CR (%): 83.81 ± 6.96 vs 88.39 ± 4.74, P = .042).In addition, GCK mRNA expression was reduced in CR patients without DM. Moreover, regression analysis indicated that the values of platelet distribution width (PDW), total cholesterol (TC), and uric acid (UA) were correlated with the incidence of CR, and hypertension lowered the CR risk. Conclusions A higher methylation of cg18492943 in GCK gene would lower the expression of GCK mRNA, which might contribute to CR in patients without DM. Meanwhile, PDW and TC might be risk factors in CR.

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GCKGene-Body Hypomethylation Is Associated with the Risk of Coronary Heart Disease

Cited by 32 publications

References 45 publications

Aberrant methylation of the GCK gene body is associated with the risk of essential hypertension

Aberrant methylation of the GCK gene body is associated with the risk of essential hypertension

TGFB2 and BCL2L11 methylation in male laryngeal cancer patients

Association ofGCKgene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients

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