scholarly journals Genetic and epigenetic associations of ANRIL with coronary artery disease and risk factors

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bayi Xu ◽  
Zhixia Xu ◽  
Yequn Chen ◽  
Nan Lu ◽  
Zhouwu Shu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Dna Methylation ◽  
Coronary Artery ◽  
Gene Dosage ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Coronary Syndrome ◽  
Non Coding Rna ◽  
Artery Disease

Abstract Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p < 0.05). The incidence of CAD, multi-vessel disease, and modified Gensini scores demonstrated a strong, direct association with ANRIL gene dosage (p < 0.05). There was no significant association between ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

scholarly journals DNA methylation of antisense noncoding RNA in the INK locus (ANRIL) is associated with coronary artery disease in a Chinese population

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chen-Hui Zhao ◽  
Hai-Tao Cao ◽  
Jing Zhang ◽  
Qiao-Wei Jia ◽  
Feng-Hui An ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Coronary Artery ◽  
Kegg Pathway ◽  
Cpg Island ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Pathway Enrichment Analysis ◽  
Artery Disease

Abstract To explore the association between methylation of antisense non-coding RNA in the INK4 locus (ANRIL) and coronary artery disease (CAD) development. Methylation levels of ANRIL in 100 subjects with CAD and 100 controls were quantitatively analyzed using Sequenom MassARRAY. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify novel pathways. Our analyses indicated that 7 to 8 CpG sites within the 2nd CpG island located upstream of ANRIL, also known as cyclin-dependent kinase inhibitor 2B – antisense 1 (CDKN2B-AS1), are hyper-methylated in CAD subjects compared to controls (p = 0.034). The 40th CpG site within the 2nd CpG island located upstream of CDKN2B-AS1 was methylated to a lesser extent in CAD subjects compared to controls (p = 0.045). Both Pearson and Spearman analyses indicated that methylation levels were significantly associated with total cholesterol (r = 0.204, p = 0.004), fasting high-density lipoprotein cholesterol (r = 0.165, p = 0.020), and fasting low-density lipoprotein cholesterol (r = 0.265, p = 0.000). KEGG pathway analysis revealed a significant enrichment of genes associated with the tumor necrosis factor (TNF) signaling pathway. Among them, CCAAT/enhancer binding protein (C/EBPβ) was identified as a key transcription factor that promotes expression of CDKN2B-AS1 through promotor interaction. DNA methylation of the ANRIL promoter was significantly associated with CAD development in our study. Our analyses suggest that C/EBPβ is a key transcription factor that promotes CDKN2B-AS1 expression by directly interacting with the gene promotor mediated by TNF signaling.

scholarly journals Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jayesh H. Prajapati ◽  
Sibasis Sahoo ◽  
Tushar Nikam ◽  
Komal H. Shah ◽  
Bhumika Maheriya ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Density Lipoprotein ◽  
Young Patients ◽  
Density Lipoprotein ◽  
High Density ◽  
Lymphocyte Ratio ◽  
Coronary Syndrome ◽  
Low Hdl ◽  
Artery Disease

Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) with high density lipoprotein (HDL) cholesterol levels in coronary artery disease (CAD) patients.Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected.Results. We have observed significant association between HDL and PLR (P=0.008) and NLR (P=0.009); however no significant relationship was obtained with HDL and isolated platelet (P=0.488), neutrophil (P=0.407), and lymphocyte (P=0.952) counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P=0.024) and NLR (P=0.03) were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3;P=0.01) and NLR (6.33 versus 5.10;P=0.01) were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P=0.007) and NLR (P=0.001) were inversely associated with HDL, whereas in older population only NLR (P=0.05) had showed a significant association.Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

Endothelial Microvesicles Circulating in Peripheral and Coronary Circulation Are Associated With Central Blood Pressure in Coronary Artery Disease

2019 ◽  
Vol 32 (12) ◽  
pp. 1199-1205 ◽  
Author(s):  
Eugenia Gkaliagkousi ◽  
Eleni Gavriilaki ◽  
Ioannis Vasileiadis ◽  
Barbara Nikolaidou ◽  
Efthalia Yiannaki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Circulation ◽  
Stable Coronary Artery Disease ◽  
Target Organ Damage ◽  
Pronounced Increase ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
Stable Cad

Abstract BACKGROUND Endothelial microvesicles (EMVs) have emerged as markers of endothelial injury. However, little is known about their levels in the coronary circulation of acute coronary syndrome (ACS) and stable coronary artery disease (CAD). We hypothesized that ACS patients exhibit a more pronounced increase of EMVs both in the peripheral and coronary circulation when compared with CAD. We also investigated possible associations of EMVs with markers preclinical target organ damage. METHODS We enrolled consecutive eligible patients undergoing coronary angiography. Blood samples were collected from the stem of the left coronary artery and the femoral artery. ΕMVs were measured by a standardized flow cytometry protocol. Central systolic blood pressure (cSBP) was measured invasively and patients’ history was recorded. RESULTS CAD patients exhibited increased levels of EMVs compared with controls. When patients with ACS and stable CAD were compared, the former had significantly increased EMVs in both coronary and peripheral circulation. Importantly, both ACS and CAD patients exhibited increased levels of EMVs in the coronary circulation compared with periphery. In addition, EMVs were associated with cSBP. CONCLUSIONS EMVs emerge as novel markers of ongoing underlying vascular damage, further augmenting the vicious cycle of inflammation and thrombosis mainly in ACS but also in stable CAD.

Abstract 14606: Endothelial Injury Biomarkers and Risk Factors Associated With Discordant Risk of Acute Coronary Syndrome Despite Controlled Low-density Lipoprotein Cholesterol Identified by a Novel Coronary Artery Disease Predictive Algorithm

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ned Premyodhin ◽  
WENJUN FAN ◽  
Masood Younus ◽  
Douglas S Harrington ◽  
Nathan D Wong
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
Predictive Algorithm ◽  
Coronary Syndrome ◽  
History Of ◽  
Artery Disease

Background: Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS who have normal LDL-C using a novel coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury validated in the Multi-Ethnic Study of Atherosclerosis cohort. Methods: Five-year predicted ACS risk was calculated using the CADPA for 8589 patients. Common risk factors and serum levels of 9 biomarkers utilized by the CADPA were tracked. We identified a “discordant high ACS” risk group with serum LDL-C < 130 mg/dL but 5-year CADPA predicted risk ≥ 7.5% and a “discordant low ACS” risk group defined as LDL-C ≥ 130 mg/dL but 5-year CADPA risk of < 7.5%. Multiple logistic regression identified risk factors and biomarkers that predicted discordance in two separate models. Results: The average age and percent male of the high ACS discordant group was higher compared to non-discordant (68±10 vs 54±13 years and 61% vs 43%, respectively). Diabetes (OR 2.84 [2.21-3.66]), male sex (OR 2.83 [2.40-3.35]), family history (OR 2.23 [1.88-2.64]) and active smoking (OR 1.99 [1.50-2.62]) exhibited greatest odds of high ACS discordance compared to other risk factors (all p < 0.01). Increased serum soluble FAS (OR 2.12 [1.97-2.29]), Hemoglobin A1c (OR 1.60 [1.48-1.72]) and interleukin-16 (OR 1.40 [1.32-1.48]) were the biomarkers most associated with discordant risk, independent of global risk factors. Conclusion: Men with diabetes and family history of myocardial infarction who are actively smoking may be at highest risk of developing ACS despite controlled LDL-C. Future studies should examine whether using the CADPA can help identify such individuals that could benefit from earlier targeting of risk factor modification for prevention of ACS.

Rheumatoid Arthritis and Coronary Artery Disease: Genetic Analyses Do Not Support a Causal Relation

2016 ◽  
Vol 44 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Henning Jansen ◽  
Christina Willenborg ◽  
Wolfgang Lieb ◽  
Lingyao Zeng ◽  
Paola Gloria Ferrario ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Inflammatory Diseases ◽  
Causal Relation ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Artery Disease

Objective.Inflammatory diseases, specifically rheumatoid arthritis (RA), are assumed to increase the risk of coronary artery disease (CAD). More recently, multiple single-nucleotide polymorphisms (SNP) associated with RA risk were identified. If causal mechanisms affecting risks of RA and CAD are overlapping, risk alleles for RA might also increase the risk of CAD.Methods.Sixty-one SNP associating with RA in genome-wide significant analyses were tested for association with CAD in CARDIoGRAM (Coronary ARtery DIsease Genome wide Replication and Meta-analysis), a metaanalysis including genome-wide association data (22,233 CAD cases, 64,762 controls). In parallel, a set of SNP being associated with low-density lipoprotein cholesterol (LDL-C) was tested as a positive control.Results.Twenty-nine RA-associated SNP displayed a directionality-consistent association with CAD (OR range 1.002–1.073), whereas 32 RA-associated SNP were not associated with CAD (OR range 0.96–0.99 per RA risk-increasing allele). The proportion (48%) of directionality-consistent associated SNP equaled the proportion expected by chance (50%, p = 0.09). Of only 5 RA-associated SNP showing p values for CAD < 0.05, 4 loci (C5orf30, IL-6R, PTPN22, and RAD51B) showed directionality-consistent effects on CAD, and 1 (rs10774624, locus SH2B3) reached study-wide significance (p = 7.29E-06). By contrast, and as a proof of concept, 46 (74%) out of 62 LDL-C–associated SNP displayed a directionality-consistent association with CAD, a proportion that was significantly different from 50% (p = 5.9E-05).Conclusion.We found no evidence that RA-associated SNP as a group are associated with CAD. Even though we were not able to study potential effects of all genetic variants individually, shared nongenetic factors may more plausibly explain the observed coincidence of the 2 conditions.

scholarly journals Temporal changes in the implementation of secondary prevention of coronary artery disease in every day practice

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
JW Peksa ◽  
P Jankowski ◽  
P Koziel ◽  
P Bogacki ◽  
P Gomula ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Body Mass Index ◽  
Coronary Artery ◽  
Confidence Intervals ◽  
Body Mass ◽  
Ldl Cholesterol ◽  
Coronary Syndrome ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf - Introduction Patients with coronary artery disease (CAD) are at high risk of recurrent cardiovascular events and control of their risk factors is crucial. Objectives Comparison of risk factors control in patients with CAD in 2016–2017 and 2011–2013. Patients and methods Five hospitals with cardiology departments serving the city and surrounding districts participated in the study. Consecutive patients hospitalized due to an acute coronary syndrome or a myocardial revascularization procedure were interviewed 6–18 months after hospitalization. The surveys were carried out in 2011–2013 and 2016–2017. Results We examined 616 patients in 2011–2013 and 388 in 2016–2017 (mean age: 64.7 ± 8.8 vs. 66.4 ± 8.4, P &lt;0.01). After adjusting for covariates the proportion of patients with high blood pressure decreased by 8.9% (95% confidence intervals: -2.1% – -15.6%) and proportion of patients with high LDL cholesterol decreased by 9.5% (-2.2% – -16.7%) in 2016/2017 compared to 2011/2013, whereas the proportion of smoking patients (-0.2% [-6.0% – 5.5%]) and those with high glucose level (3.9% [-2.2% - 10.0%]) and with body mass index ≥25 kg/m2 (3.8% [-3.9% – 11.6%]) did not change significantly. The proportion of patients prescribed antiplatelets (6.5% [2.6% - 10.3%]), β-blockers (7.4% [2.2% - 12.6%]), angiotensin converting enzyme inhibitors or sartans (8.6% [2.9% – 14.3%]), calcium antagonists (8.1% [1.3 – 15.0]) and anticoagulants (5.5% [0.7% - 10.2%]) increased significantly. Conclusions In CAD patients, there was an increase of the proportion of patients with cardiovascular drugs prescribed and a slight improvement in the control of blood pressure and LDL cholesterol between 2011–2013 and 2016–2017. However, no significant changes were found for the other main risk factors. Patients who do not reach treatment goal Survey Smoking, % BP not at goal, %a BP ≥140/90 mmHg, % LDL cholesterol ≥1.8 mmol/l, % HbA1c ≥7.0%b, % Fasting glucose ≥7.0 mmol/l, % BMI≥25 kg/m2, % BMI≥30 kg/m2, % 2011-2013 19.0 50.3 43.0 71.9 14.1 15.9 81.2 33.8 2016-2017 16.2 40.7 39.2 60.3 14.9 20.2 83.4 38.3 P value 0.26 &lt;0.01 0.24 &lt;0.001 0.76 0.09 0.37 0.14 Differences adjusted for age, sex, index diagnosis, duration of education, professional activity (95% confidence intervals) 2016-2017 vs 2011-2013 -0.2(-6.0 - 5.5) -8.9(-15.6 - -2.1) -6.7(-14.3 - 1.0) -9.5(-16.7 - -2.2) 2.0(-3.4 - 7.4) 3.9(-2.2 - 10.0) 3.8(-3.9 - 11.6) 1.6 (-5.8 - 9.0) Abbreviations BMI, body mass index; BP, blood pressure; LDL, low-density lipoprotein a BP goal of &lt;140/90mmHg (&lt;130/80 mmHg in diabetics) in 2011–2013 and &lt;140/90 mmHg (&lt;140/85 mmHg in diabetics) in 2016–2017 b available for 362 patients in 2011-2013 and 383 patients in 2016-2017

scholarly journals Polymorphisms of rs2483205 and rs562556 in the PCSK9 gene are associated with coronary artery disease and cardiovascular risk factors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Min-Tao Gai ◽  
Dilare Adi ◽  
Xiao-Cui Chen ◽  
Fen Liu ◽  
Xiang Xie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Blood Glucose ◽  
Coronary Artery ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Nucleotide Polymorphisms ◽  
Pcsk9 Gene ◽  
Increased Risk ◽  
Artery Disease

AbstractPCSK9 plays a crucial role in lipid metabolism. This case–control study explored the associations of novel single nucleotide polymorphisms (SNPs) of the PCSK9 gene with coronary artery disease (CAD) (≥ 1 coronary artery stenosis ≥ 50%) and its risk factors in the Han population in Xinjiang, China. Four tag SNPs (rs11583680, rs2483205, rs2495477 and rs562556) of the PCSK9 gene were genotyped in 950 CAD patients and 1082 healthy controls. The distributions of genotypes in rs2483205 and rs562556 were significantly different between the groups (all p < 0.05). The TT genotype of rs2483205, GG genotype of rs562556, and their H4 (T-G) haplotype were associated with CAD [odds ratio (OR) 0.65, confidence interval (CI) 0.45–0.95, p = 0.024; 0.63, 0.45–0.90, p = 0.011; 0.50, 0.35–0.70, p < 0.001, respectively]. Additionally, the model (TT + CT vs. CC) of rs2483205 was associated with increased risk of obesity, and the G allele of rs562556 was associated with lower low-density lipoprotein cholesterol (LDL-C), blood glucose, body mass index (BMI), and mean platelet volume (MPV) (all p < 0.05). rs2483205, rs562556, and their H4 haplotype of the PCSK9 gene were associated with CAD. Additionally, rs2483205 is associated with obesity, and rs562556 is associated with LDL-C, blood glucose, BMI, and MPV.

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