Allele-specific methylation contributed by CpG-SNP is associated with regulation of ALOX5AP gene expression in ischemic stroke

Shi, Yunshu; Xu, Liyan; Feng, Qingchuan; Li, Aifan; Jia, Jizeng; Xu, Yan; Yang, Dongzhi; Zhang, Yuchao; Zhang, Xuran; Zhao, Hang; Wang, Jun; He, Ying; Zheng, Hong

doi:10.1007/s10072-018-3489-9

Cited by 5 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of CVDs, the PEAR1 gene and ALOX5AP gene have been associated with the disease [19, 116]. PEAR1, as discussed earlier, plays a role in cardiovascular events.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review

Vohra

Sharma

et al. 2020

Public Health Genomics

View full text Add to dashboard Cite

Introduction: The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population migrations, genetic drift, and selection. Although there are a plethora of DNA sequence variations identified through genome-wide association studies (GWAS), the challenge remains to explain the mechanisms underlying interindividual phenotypic disparity accounting for disease susceptibility. Single nucleotide polymorphisms (SNPs) present in the sites for DNA methylation, transcription factor (TF) binding, or miRNA targets can alter the gene expression. The systematic review aimed to evaluate the complex crosstalk among SNPs, miRNAs, DNA methylation, and TFs for complex multifactorial disease risk. Methods: PubMed and Scopus databases were used from inception until May 15, 2019. Initially, screening of articles involved studies assessing the interaction of SNPs with TFs, DNA methylation, or miRNAs resulting in allele-specific gene expression in complex multifactorial diseases. We also included the studies which provided experimental validation of the interaction of SNPs with each of these factors. The results from various studies on multifactorial diseases were assessed. Results: A total of 11 articles for SNPs interacting with DNA methylation, 30 articles for SNPs interacting with TFs, and 11 articles for SNPs in miRNA binding sites were selected. The interactions of SNPs with epigenetic factors were found to be implicated in different types of cancers, autoimmune diseases, cardiovascular diseases, diabetes, and asthma. Conclusion: The systematic review provides evidence for the interplay between genetic and epigenetic risk factors through allele-specific gene expression in various complex multifactorial diseases.

show abstract

“…In the case of CVDs, the PEAR1 gene and ALOX5AP gene have been associated with the disease [19, 116]. PEAR1, as discussed earlier, plays a role in cardiovascular events.…”

Section: Resultsmentioning

confidence: 99%

“…The ALOX5AP gene codes for 5-lipoxygenase-activating protein and is a risk factor for ischemic stroke. Two CpG SNPs, namely, rs12041331 in the PEAR1 gene and rs4073259 in the ALOX5AP gene, affect the expression of genes through allele-specific methylation and contribute to platelet reactivity and ischemic stroke, respectively [19, 116].…”

Section: Resultsmentioning

confidence: 99%

SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review

Vohra

Sharma

et al. 2020

Public Health Genomics

View full text Add to dashboard Cite

show abstract

“…Of note, the methylation levels of CpG8 were significantly different from other sites due to the generation of a CpG site. In a previous study conducted by our group, IS-associated CpG-SNP rs4073259 correlated with differential DNA methylation, presenting the phenomenon of allele-specific methylation which may elucidate the phenotypic effects of certain genetic variants ( 25 ).…”

Section: Discussionmentioning

confidence: 94%

Epigenetic regulation mechanism of DNA methylation and miRNAs on the expression of the ALOX5AP gene in patients with ischemic stroke

et al. 2021

Self Cite

View full text Add to dashboard Cite

5-lipoxygenase-activating protein (FLAP), encoded by the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene, can adjust the biogenesis of proinflammatory leukotrienes to increase the adhesion and permeability of the vascular internal wall. Moreover, it participates in the process of atherosclerosis and is closely associated with ischemic stroke (IS). Accumulating evidence has shown that the expression levels of the ALOX5AP gene are upregulated in patients with IS. However, the mechanism of ALOX5AP action in IS remain elusive. The present study hypothesized that epigenetic regulation, including DNA methylation and microRNA (miR/miRNA) regulation, affects the expression levels of the ALOX5AP gene. Therefore, 200 patients with a first diagnosis of acute IS and 200 healthy control subjects were enrolled in the present study. Initially, the mRNA expression levels of the ALOX5AP gene were examined by reverse transcription-quantitative PCR. It was found that the mRNA levels of ALOX5AP gene in the IS group were significantly higher compared with controls (P<0.05). Subsequently, the methylation status of 17 CpG sites located in the promoter region of ALOX5AP was assessed by MethyTarget sequencing.However, the levels of methylation exhibited no significant differences between IS and control groups (P>0.05). Moreover, the expression levels of miR-335 and miR-495 were examined as two potential miRNAs targeting the ALOX5AP gene. The expression levels of miR-335 and miR-495 in the IS group were significantly lower compared with the control group (P<0.05). Finally, the luciferase assay results indicated that the luciferase activity of the experimental group following co-transfection of miRNA mimic and wild-type reporter gene plasmid was significantly lower compared with the other experimental groups (P<0.05), suggesting that miR-335 and miR-495 could specifically bind to the 3'-untranslated region of the ALOX5AP gene, thereby downregulating its expression. The present study provided preliminary evidence demonstrating that epigenetic regulation affects the expression of the ALOX5AP gene in patients with IS.

show abstract

“…After duplicates were removed, 176 studies remained. On examination of the full text, 30 papers were eligible for inclusion in the review 11–40. Study selection is shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, four Asian studies providing summaries of data on the ALOX5AP rs4073259 polymorphism did not find any association with IS risk (OR=1.20 for A allele vs G allele; 95% CI: 1.00–1.45; P =0.056) (Table 2). 21,30,40…”

Section: Resultsmentioning

confidence: 99%

<p>Lack of association between <em>ALOX5AP</em> genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses</p>

Zheng¹,

Ning²,

Xu³

et al. 2019

NDT

View full text Add to dashboard Cite

BackgroundIn recent years, there has been substantial research evaluating the relationship between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) polymorphisms and ischemic stroke (IS). The objective of this study was to systematically review and analyze the existing evidence.MethodsA comprehensive search of major electronic databases for studies published between 1990 and 2018 was carried out. Data were synthesized as OR and 95% CI using fixed-effects and random-effects models.ResultsA total of 30 studies were available for analysis. The aggregate sample size across all studies was 32,782 (16,294 cases and 16,488 controls). We found no association of the ALOX5AP rs10507391 (OR=1.03 for A allele vs T allele; 95% CI: 0.93–1.14; P=0.557), rs4769874 (OR=1.13 for A allele vs G allele; 95% CI: 1.00–1.28; P=0.050), rs9551963 (OR=1.03 for A allele vs C allele; 95% CI: 0.96–1.11; P=0.372), rs17222814 (OR=1.09 for A allele vs G allele; 95% CI: 0.96–1.24; P=0.195), rs17222919 (OR=0.89 for G allele vs T allele; 95% CI: 0.75–1.06; P=0.175), and rs4073259 (OR=1.20 for A allele vs G allele; 95% CI: 1.00–1.45; P=0.056) polymorphisms with IS risk. Haplotype analysis also did not yield significant findings for the HapA (rs17222814G–rs10507391T–rs4769874G–rs9551963A; OR=1.20; 95% CI: 0.91–1.56; P=0.192) and HapB (rs17216473A–rs10507391A–rs9315050A–rs17222842G; OR=1.11; 95% CI: 0.90–1.38; P=0.339) haplotypes.ConclusionCurrent evidence does not support an association of rs10507391, rs4769874, rs9551963, rs17222814, rs17222919, rs4073259, and HapA and HapB with IS risk.

show abstract

Allele-specific methylation contributed by CpG-SNP is associated with regulation of ALOX5AP gene expression in ischemic stroke

Cited by 5 publications

References 26 publications

SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review

SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review

Epigenetic regulation mechanism of DNA methylation and miRNAs on the expression of the ALOX5AP gene in patients with ischemic stroke

<p>Lack of association between <em>ALOX5AP</em> genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses</p>

Contact Info

Product

Resources

About