Elevated PLA2G7 Gene Promoter Methylation as a Gender-Specific Marker of Aging Increases the Risk of Coronary Heart Disease in Females

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

doi:10.1371/journal.pone.0059752

Cited by 78 publications

(64 citation statements)

References 51 publications

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“…70 A follow-up candidate gene study with TNNT1 found that in individuals without familial hypercholesterolemia, increased methylation was associated with CAD. 71 In other candidate gene studies, increased methylation at CDKN2B was associated with CAD, 72 increased methylation at PLA2G7 was associated with CAD among women, 73 and increased methylation at INS and GNASAS, loci with a methylation status thought to be influenced by the prenatal environment, was associated with increased incidence of MI among women. 74 Although all of these findings are intriguing, for the most part, they have emerged from small sample sizes and need to be replicated in independent cohorts to establish their validity.…”

Section: Musunuru Et Al Expressed Genome In Cardiovascular Diseases Amentioning

confidence: 88%

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

Musunuru¹,

Ingelsson²,

Fornage³

et al. 2017

Circ Cardiovasc Genet

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Abstract-There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the "expressed genome." The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias. (Circ Cardiovasc Genet. 2017;10:e000037. DOI: 10.1161/HCG.0000000000000037.)Key Words: AHA Scientific Statements ◼ cardiovascular diseases ◼ DNA ◼ epigenomics ◼ genome ◼ metabolomics ◼ proteomics ◼ strokeThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on March 13, 2017, and the American Heart Association Executive Committee on April 17, 2017. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The American Heart Association requests that this document be cited as follows: Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development."Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/CopyrightPermission-Guidelines_UCM_300404_Article.jsp. A link to the "Copyright Permissions Request Form" appears on the right side of the page. I n no small part as a result of the completion of the Human Genome Project, considerable effort has been invested over the past few decades in understanding the contribution of genetics to the risk of cardiovascular diseases and stroke. Genomewide association studies, candidate gene sequencing studies, a...

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Section: Musunuru Et Al Expressed Genome In Cardiovascular Diseases Amentioning

confidence: 88%

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

Musunuru¹,

Ingelsson²,

Fornage³

et al. 2017

Circ Cardiovasc Genet

View full text Add to dashboard Cite

show abstract

“…In certain types of human tissue, positive correlation between gene-body methylation and gene expression has been identified (34,35). Gene-body methylation was reported to be significant in regulating cell context-specific alternative promoters in human and mouse tissues (28).…”

Section: Discussionmentioning

confidence: 99%

“…Plasma levels of cholesterol, triglyceride (TG), alanine transaminase (ALT), aspartate transaminase, uric acid and glucose concentrations were enzymatically measured using a CX7 biochemical analyzer (Beckman Coulter, Brea, CA, USA). DNA methylation was measured using sodium bisulphite DNA conversion coupled with pyrosequencing (28). Briefly, genomic DNA was chemically modified by sodium bisulphite (EpiTech Bisulphite kit; Qiagen, Hilden, Germany) to convert all the unmethylated cytosines into uracils, while the methylated cytosines remained unchanged.…”

Section: Introductionmentioning

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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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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“…Secondly, a fragment that contains only five CpG sites in the DRD4 promoter was tested in the present study and this fragment may not be sufficient to reflect the DNA methylation state of the whole gene. Thirdly, tissue specificity between the peripheral blood and brain still needs to be taken into account, although a strong correlation of gene methylation between the blood and brain has previously been observed (36). Lastly, a functional study of the target sequence on the RNA and the protein expression levels was not performed due to a lack of samples.…”

Section: P-value Subgroups ------------------------------------------mentioning

confidence: 99%

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

Liu

et al. 2017

Exp Ther Med

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Abstract. Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (P<0.05). Male METH addicts exhibited significantly higher DRD4 CpG1, CpG2 and CpG4 methylation levels compared with sex-matched controls (P<0.05). In heroin addicts, a positive correlation was observed between depression-dejection and DRD4 CpG5 methylation (r=0.537, P=0.039) whereas there was a negative correlation between drug usage frequency and CpG1 methylation (r=-0.632, P=0.011). In METH addicts, methylation levels were not significantly associated with depression-dejection and drug usage frequency. In addition, luciferase assays demonstrated that the target sequence of the DRD4 promoter upregulates gene expression. The results of the present study suggest that DNA methylation of DRD4 may be responsible for the pathophysiology of drug addiction.

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Elevated PLA2G7 Gene Promoter Methylation as a Gender-Specific Marker of Aging Increases the Risk of Coronary Heart Disease in Females

Cited by 78 publications

References 51 publications

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

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

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

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