The association of single nucleotide polymorphism rs189037C&gt;T in ATM gene with coronary artery disease in Chinese Han populations

Ding, Xiang; He, Yong; Qin, Hao; Chen, Shanping; Yang, Ming; Leng, Sean X.; Yue, Jirong; Dong, Birong

doi:10.1097/md.0000000000009747

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…NLRC4 and NCL contain genetic variants associated with inflammation biomarkers [ 28 , 29 ]. Genetic variants in PTEN and ATM genes have been associated with eosinophil count [ 30 ] and CHD [ 31 ], respectively. Finally, differential methylation in cg06642177 linked to SKG1 has been previously associated with myocardial infarction [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation and gene expression integration in cardiovascular disease

et al. 2021

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Background The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. Results Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. Conclusions Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

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Section: Discussionmentioning

confidence: 99%

DNA methylation and gene expression integration in cardiovascular disease

et al. 2021

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“…D’Ascenzo et al found that the inhibition of STAT3 phosphorylation attenuated ischemia–reperfusion injury during interventional therapy for acute coronary syndrome ( 38 ). Additionally, in Chinese Han populations, the ATM rs189037 polymorphism is associated with coronary artery disease (CAD), and the rs189037 genotype seems to be associated with a lower risk of CAD and is a protective genetic marker of CAD, particularly in males and smokers ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy

Huang

Mei

Duan

et al. 2023

Front. Cardiovasc. Med.

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BackgroundCardiomyocyte death is an important pathophysiological basis for ischemic cardiomyopathy (ICM). Many studies have suggested that ferroptosis is a key link in the development of ICM. We performed bioinformatics analysis and experiment validation to explore the potential ferroptosis-related genes and immune infiltration of ICM.MethodsWe downloaded the datasets of ICM from the Gene Expression Omnibus database and analyzed the ferroptosis-related differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein–protein interaction network were performed to analyze ferroptosis-related DEGs. Gene Set Enrichment Analysis was used to evaluate the gene enrichment signaling pathway of ferroptosis-related genes in ICM. Then, we explored the immune landscape of patients with ICM. Finally, the RNA expression of the top five ferroptosis-related DEGs was validated in blood samples from patients with ICM and healthy controls using qRT-PCR.ResultsOverall, 42 ferroptosis-related DEGs (17 upregulated and 25 downregulated genes) were identified. Functional enrichment analysis indicated several enriched terms related to ferroptosis and the immune pathway. Immunological analysis suggested that the immune microenvironment in patients with ICM is altered. The immune checkpoint-related genes (PDCD1LG2, LAG3, and TIGIT) were overexpressed in ICM. The qRT-PCR results showed that the expression levels of IL6, JUN, STAT3, and ATM in patients with ICM and healthy controls were consistent with the bioinformatics analysis results from the mRNA microarray.ConclusionOur study showed significant differences in ferroptosis-related genes and functional pathway between ICM patients and healthy controls. We also provided insight into the landscape of immune cells and the expression of immune checkpoints in patients with ICM. This study provides a new road for future investigation of the pathogenesis and treatment of ICM.

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“…As a regulator of oxidative stress and sensor of DNA damage, ATM gene prevents cellular senescence, death, or cell cycle arrest; in addition, it protects individuals from ROS-induced DNA damage. Ding et al have described an association of SNP rs189037 in ATM gene with the proportion of coronary artery disease in Chinese Han population and demonstrated a low proportion of coronary artery disease in participants harboring TT genotype ( 21 ). In the current study, the young and centenarian participants showed significantly lower frequency of mutant rs189037 in ATM gene than middle-aged and elderly participants.…”

Section: Discussionmentioning

confidence: 99%

Mutant Single Nucleotide Polymorphism rs189037 in Ataxia-Telangiectasia Mutated Gene Is Significantly Associated With Ventricular Wall Thickness and Human Lifespan

Chen

et al. 2021

Front. Cardiovasc. Med.

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In the current study, we aimed to determine the association of single nucleotide polymorphism rs189037 in ataxia-telangiectasia mutated (ATM) gene with cardiac structure and human longevity. Based on the China Hainan Centenarian Cohort Study performed in 18 cities and counties of Hainan Province, China, the current study enrolled 547 centenarians, 250 young participants aged 20–45 years, and 250 middle-aged and elderly participants aged 46–90 years. The frequency of TT genotype was significantly higher and that of CC genotype was significantly lower in middle-aged and elderly participants than in young (P = 0.012) and centenarian (P = 0.041) participants. There were no significant differences in the genotype and allele frequencies of SNP rs189037 between young and centenarian participants. Compared with CT genotype, TT genotype was positively and significantly associated with interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in centenarian (IVST: P = 0.049; LVPWT: P = 0.047) and middle-aged and elderly (IVST: P = 0.008; LVPWT: P = 0.004) participants. Compared with CC genotype, TT genotype was positively and significantly associated with LVPWT in centenarian (P = 0.030) and middle-aged and elderly (P = 0.013) participants. Compared with CC genotype, CT genotype was negatively and significantly associated with left ventricular end-diastolic diameter (LVEDD) in centenarian (P = 0.011) and middle-aged and elderly (P = 0.040) participants. The current study demonstrated that mutant rs189037 in the ATM gene was more commonly identified in middle-aged and elderly participants than in young and centenarian participants, was significantly associated with increased left ventricular wall thickness and volume, and could induce left ventricular eccentric hypertrophy and shorten human lifespan. Therefore, rs189037 without mutation might be an indicator of youth health and successful aging, whereas mutant rs189037 might hinder human longevity.

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The association of single nucleotide polymorphism rs189037C>T in ATM gene with coronary artery disease in Chinese Han populations

Abstract: Supplemental Digital Content is available in the text

Cited by 12 publications

References 42 publications

DNA methylation and gene expression integration in cardiovascular disease

DNA methylation and gene expression integration in cardiovascular disease

Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy

Mutant Single Nucleotide Polymorphism rs189037 in Ataxia-Telangiectasia Mutated Gene Is Significantly Associated With Ventricular Wall Thickness and Human Lifespan

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