Altered expression of lysosomal hydrolase, acid α-glucosidase, gene in coronary artery disease

Zhang, Jingyi; Ma, Ling; Zhang, Junping; Huang, Jian; Wei, Guanghe; Liu, Lixin; Zhang, Jinguo; Yan, Bo

doi:10.1097/mca.0000000000000322

Cited by 7 publications

(3 citation statements)

References 31 publications

(33 reference statements)

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“…The CBX gene family, a recent research interest in the field of long noncoding RNAs, has been associated with CVD and atherosclerosis in multiple studies [25,26]. GAA gene expression has been found to be specifically increased in CAD patients than in controls [27]. CARD14, which is mainly associated with psoriasis (ongoing clinical studies suggest increased risk of CVDs in psoriasis) and auto-inflammatory disorders, acts as a pro-inflammatory gene by affecting NF-kB activation in the IL-17 inflammation pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

et al. 2021

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Background Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients. Methods We conducted a genome-wide association study (GWAS) of a multiple case–control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case–control group with 7,975,321 imputed single nucleotide polymorphisms using the Phase 3 Asian panel from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci. Results Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]). Conclusions This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

et al. 2021

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“…However, it has been found that aberrant expression of hsa-miR-139-5p could lead to apoptosis [ 26 ] which has been observed in coronary atherosclerosis [ 27 ]. hsa-miR-502-5p has been reported to inhibit autophage [ 28 ] and the alteration of autophagic genes has also be discovered in CAD [ 29 ]. So, these three miRNAs could play an important role in CAD.…”

Section: Discussionmentioning

confidence: 99%

Identification of key miRNAs and mRNAs related to coronary artery disease by meta-analysis

Liu

Zhang

et al. 2021

BMC Cardiovasc Disord

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Background To illustrate the mechanism of miRNA and mRNA in coronary artery diseasen (CAD), differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. Methods The mRNA transcription profiles of GSE20680 (including 87 blood samples of CAD and 52 blood samples of control), GSE20681 (including 99 blood samples of CAD and 99 blood samples of control) and GSE12288 (including 110 blood samples of CAD and 112 blood samples of control) and the miRNA transcription profiles of GSE59421 (including 33 blood samples of CAD and 37 blood samples of control), GSE49823 (including 12 blood samples of CAD and 12 blood samples of control) and GSE28858 (including 13 blood samples of CAD and 13 blood samples of control) were downloaded from Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/). Then, the homogenous expressed mRNAs and miRNAs across the three mRNA transcription profiles and three miRNA transcription profiles were screened using the Fishers exact test in MetaDE. ES package. The weighted gene co-expression network analysis (WGCNA) was used to analyze gene modules. Additionally, the integrated miRNAs–targets regulatory network using the DEmiRNA and their targets was constructed using Cytoscape. Results A total of 1201 homogenously statistically significant DEGs were identified including 879 up-regulated and 322 down-regulated DEGs, while a total of 47 homogenously statistically significant DEmiRNAs including 37 up-regulated and 10 down-regulated DEmiRNAs in CAD compared with the controls across the three mRNA transcription profiles and the three miRNA transcription profiles. A total of 5067 genes were clustered into 9 modules in the training dataset, among which, 8 modules were validated. In the miRNAs-targets network, there existed 267 interaction relationships among 5 miRNAs (hsa-miR-361-5p, hsa-miR-139-5p, hsa-miR-146b-5p, hsa-miR-502-5p and hsa-miR-501-5p) and 213 targets. CAV1 could be the target of hsa-miR-361-5 while HSF2 was the target of both hsa-miR-361-5p and hsa-miR-146b-5p. CAV1 was significantly enriched in the GO term of regulation of cell proliferation. Conclusion hsa-miR-361-5p, has-miR-146b-5p, CAV1 and HSF2 could play an important role in CAD.

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“…[24,25] GAA gene expression has been found to be speci cally increased in CAD patients than in controls. [26] CARD14, which is mainly associated with psoriasis (ongoing clinical studies suggest increased risk of CVDs in psoriasis) and auto-in ammatory disorders, acts as a pro-in ammatory gene by affecting NF-kB activation in the IL-17 in ammation pathway. Puig et al [27] found that expression of genes such as CARD14 classi ed human atherosclerotic plaque by relative in ammation status.…”

Section: Discussionmentioning

confidence: 99%

Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia 

Song

Choi

Kwon

et al. 2020

Preprint

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Background: Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients.Methods: We conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using Phase 1/2 Asian panels from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci.Results: Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]).Conclusions: This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

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Altered expression of lysosomal hydrolase, acid α-glucosidase, gene in coronary artery disease

Abstract: Compared with controls, GAA gene expression levels in CAD patients were significantly increased, suggesting that GAA may be involved in the CAD development.

Cited by 7 publications

References 31 publications

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

Identification of key miRNAs and mRNAs related to coronary artery disease by meta-analysis

Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia

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Altered expression of lysosomal hydrolase, acid α-glucosidase, gene in coronary artery disease

Abstract: Compared with controls, GAA gene expression levels in CAD patients were significantly increased, suggesting that GAA may be involved in the CAD development.

Cited by 7 publications

References 31 publications

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

Identification of key miRNAs and mRNAs related to coronary artery disease by meta-analysis

Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia&nbsp;

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Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia