scholarly journals Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muneeza Zafar ◽  
Munazza Raza Mirza ◽  
Fazli Rabbi Awan ◽  
Muhammad Tahir ◽  
Rabia Sultan ◽  
...  

AbstractIn the current study, APOB (rs1052031) genotype-guided proteomic analysis was performed in a cohort of Pakistani population. A total of 700 study subjects, including Coronary Artery Disease (CAD) patients (n = 480) and healthy individuals (n = 220) as a control group were included in the study. Genotyping was carried out by using tetra primer-amplification refractory mutation system-based polymerase chain reaction (T-ARMS-PCR) whereas mass spectrometry (Orbitrap MS) was used for label free quantification of serum samples. Genotypic frequency of GG genotype was found to be 90.1%, while 6.4% was for GA genotype and 3.5% was for AA genotypes in CAD patients. In the control group, 87.2% healthy subjects were found to have GG genotype, 11.8% had GA genotype, and 0.9% were with AA genotypes. Significant (p = 0.007) difference was observed between genotypic frequencies in the patients and the control group. The rare allele AA was found to be strongly associated with the CAD [OR: 4 (1.9–16.7)], as compared to the control group in recessive genetic model (p = 0.04). Using label free proteomics, altered expression of 60 significant proteins was observed. Enrichment analysis of these protein showed higher number of up-regulated pathways, including phosphatidylcholine-sterol O-acyltransferase activator activity, cholesterol transfer activity, and sterol transfer activity in AA genotype of rs562338 (G>A) as compared to the wild type GG genotype. This study provides a deeper insight into CAD pathobiology with reference to proteogenomics, and proving this approach as a good platform for identifying the novel proteins and signaling pathways in relation to cardiovascular diseases.

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Chandan k Jha ◽  
Jamsheed Javid ◽  
Suriya Rehman ◽  
...  

Aim: Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of the coronary artery diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases. Methodology: This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using amplification refractory mutation system PCR method (ARMS-PCR). Results: The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95 % CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95 % CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95 % CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusion: Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with an increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.P Dias Ferreira Reis ◽  
R Ramos ◽  
P Modas Daniel ◽  
S Aguiar Rosa ◽  
L Almeida Morais ◽  
...  

Abstract Aim In patients (pts) with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) may improve pt selection for invasive coronary angiography (ICA) as alternative to functional testing. However. the role of CTA in symptomatic pts after abnormal functional test (FT) is incompletely defined. Methods and results This randomized clinical trial conducted in single academic tertiary center selected 218 symptomatic pts with mild to moderately abnormal FT referred to ICA to receive either the originally intended ICA (n=103) or CTA (n=115). CTA interpretation and subsequent care decisions were made by the clinical team. Pts with high risk features on FT, previous acute coronary syndrome, previously documented CAD, chronic kidney disease (GFR<60ml/min/1.73m2) or persistent atrial fibrillation were excluded. The primary endpoint was the percentage of ICA with no significant obstructive CAD (no stenosis ≥50%) in each group. Diagnostic (DY) and revascularization (RY) yields of ICA in either group were also assessed. Pts were followed up for at least 1 year for the primary safety endpoint of all cause death/ nonfatal myocardial infarction/ stroke. Unplanned revascularization (UP) and symptomatic status (SS) were also evaluated. Pts averaged 68±9 years of age, 60% were male, 29% were diabetic. Nuclear perfusion stress test was used in 33.9% in CTA group and 31.1% in control group (p=0.655). Mean post (functional) test probability of obstructive CAD was 34%. Overall prevalence of obstructive CAD was 32.1%. In the CTA group, ICA was cancelled by referring physicians in 83 of the pts (72.2%) after receiving CTA results. For those undergoing ICA, non-obstructive CAD was found in 5 pts (15.6%) in the CTA-guided arm and 60 (58.3%) in the usual care arm (p<0.001 Mean cumulative radiation exposure related to diagnostic work up was similar in both groups (6±14 vs 5±14mSv, p=0.152). Both DY (84.4% vs 41.7, p<0.001) and RY (71.9% vs 38.8%, p=0.001) yields were significantly higher for CTA-guided ICA as compared to standard FT-guided ICA. The rate of the primary safety endpoint was similar between both groups (1.9% vs 0%, p=0.244), as well as the rates of UP (0.9% vs 0.9%, p=1.000) and SS (persistent angina: 29.6% vs 24.8%, p=0.425). Conclusions In pts with suspected CAD and mild to moderately abnormal ischemia test, a diagnostic strategy including CTA as gatekeeper is safe, effective and significantly improves diagnostic and revascularization yields of ICA. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 20 (7) ◽  
pp. 3077
Author(s):  
M. A. Kokozheva ◽  
B. U. Mardanov ◽  
E. A. Poddubskaya ◽  
V. A. Kutsenko ◽  
M. A. Umetov ◽  
...  

Aim. To study the structural and functional myocardial characteristics in patients with exertional angina and type 2 diabetes in comparison with those without diabetes to identify combined hemodynamic changes.Material and methods. Patients were divided into two groups depen - ding on the glycemic status. The first group consisted of 49 patients (mean age, 57,9±1,04 years; male/female, 35/14) with coronary artery disease (CAD) and type 2 diabetes, while the second one (control)  — 51 patients (60,2±0,9 years, 34/17) with CAD and without diabetes. Patients were surveyed using a standard questionnaire that included socio-demographic parameters, behavioral risk factors, clinical status, medications received, and comorbidities. Diagnostic investigations were carried out, including resting electrocardiography, transthoracic echocardiography and cycle ergometry.Results. Among patients with CAD and type 2 diabetes, hypertension occurred 20% more often compared with the control group  — 98 vs 78% (p<0,004). According to the electrocardiography, the combination of diabetes and CAD was characterized by various arrhythmias, which were recorded 2,8 times more often than in the group without diabetes. According to echocardiography, signs of left ventricular hypertrophy, systolic and diastolic dysfunction prevailed in people with diabetes. Mean pulmonary artery pressure in patients with diabetes were higher than in patients without carbohydrate metabolism disorders (p<0,004). According to the stress test, exercise tolerance in experimental group patients was lower than in patients in the control group.Conclusion. The combination of chronic CAD and type 2 diabetes is cha - racterized by a more common combination with hypertension, impaired central and intracardiac hemodynamics, as well as left ventricular hypertrophy. In people with diabetes, impaired systolic and diastolic myocardial function is combined with reduced exercise tolerance.


2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Palisha Alimu ◽  
Dezhi Yang ◽  
Huatao Zhou ◽  
Yan Wu ◽  
Huiping Guo

Background. Arrhythmia is one of the causes of death in severe coronary artery disease patients who also suffered from cancer. Our research aims to compare the incidence of arrhythmia between severe coronary artery disease patient with and without new-onset tumor. Methodology. We enrolled 79 patients (December 2019–December 2020) with severe coronary artery disease in this study, and 40 of them were complicated with new-onset tumor. The details of all subjects were thoroughly obtained; the laboratory tests were implemented including creatinine before coronary angiography. The appraisal of the severity of coronary artery disease was applied by Gensini score. The cardiac inspection includes UCG, 12-lead ECG, and Holter monitor. Results. Among them, there were 40 patients in the experimental group and 39 patients in the control group. The difference at the baseline between the two sets of figures was not statistically significant ( P > 0.05 ). The incidence of arrhythmia between the two groups was statistically significant ( P < 0.05 ). Conclusions. The incidence of arrhythmia in severe coronary artery disease patients who were complicated with new-onset tumor was higher than that in patients with severe coronary artery disease alone, and attention should be paid to arrhythmia before tumor treatment.


Author(s):  
Thangam Menon ◽  
Supraja Kalyanaraman ◽  
Seethalakshmi Srinivasan

Introduction: Distinct microbial communities reside in the oral cavity and the composition of the oral microbiota has important implications for human health and disease. Identification of bacterial flora of the microbiome is done by metagenomic analysis of 16S ribosomal RNA sequences. Aim: The aim of this study was to characterise the human microbiome in patients with Coronary Artery Disease (CAD) in comparison with the normal human microbiome. Materials and Methods: A pilot study was carried out in tertiary hospital, Chennai. Oral mouthwash samples collected from nine patients with CAD were selected, with one control group. They were studied by metagenomic analysis of V3-V4 region of 16SrRNA gene sequences.. Sequencing of the variable V3 and V4 regions was done using Illumina platform. Results: The six major phyla, Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes, and Fusobacteriacontained 99% of the taxa in all the samples analysed. Conclusion: Diversity of the microbiome in patients with CAD was similar to the normal human microbiome.


2021 ◽  
Author(s):  
Afek Kodesh ◽  
Eli Lev ◽  
Dorit Leshem-Lev ◽  
Alejandro Solodky ◽  
Ran Kornowski ◽  
...  

Abstract Purpose: Calcium channel blockers (CCBs) do not reduce the risk of initial or recurrent myocardial infarction (MI) in patients diagnosed with stable coronary artery disease (CAD). The aim of this current study was to evaluate the association between CCBs and aspirin resistance in patients with CAD. Methods: Patients with stable CAD who were regularly taking aspirin (75-100 mg qd) for at least one month prior to enrollment in the study were included. The VerifyNow system was used for platelet function testing with high on-aspirin platelet reactivity (HAPR) defined as aspirin reaction units (ARU) >550. We compared patients treated with CCBs versus control group. Results: 503 patients with CAD were included in this study, 88 were treated with CCBs; Mean age (67.9±9.7 in the CCB group vs 66.5±11.4 in the control group, p=0.288), gender (77.3 male vs. 82.9%, p=0.214) and rates of diabetes mellitus (34.7 vs. 36.9%, p=.121) were similar. Rates of hypertension were higher in the CCB group (83.9 vs. 63.5%, p<0.01), but rates of past MI were lower (47.1 vs. 59.7%, p=0.039). The mean ARU was 465.4P70.0 for patients treated with CCBs versus 445.2u60.0 in controls (p=0.006). Similarly, 15.9% of CCB patients demonstrated HAPR compared to 7.0% (p=0.006). In a multivariate analysis, the administration of CCBs was independently associated with HAPR (OR- 1.72, 95% CI 1.04 – 8.91, p=0.047). Conclusions: Usage of CCBs is positively correlated with aspirin resistance. These findings may suggest an adverse pharmacologic effect of CCBs among patients with stable CAD treated with aspirin.


2016 ◽  
Vol 48 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Monique Mendelson ◽  
Owen D. Lyons ◽  
Azadeh Yadollahi ◽  
Toru Inami ◽  
Paul Oh ◽  
...  

Overnight fluid shift from the legs to the neck and lungs may contribute to the pathogenesis of obstructive sleep apnoea (OSA) and central sleep apnoea (CSA). We hypothesised that exercise training will decrease the severity of OSA and CSA in patients with coronary artery disease (CAD) by decreasing daytime leg fluid accumulation and overnight rostral fluid shift.Patients with CAD and OSA or CSA (apnoea–hypopnoea index >15 events per h) were randomised to 4 weeks of aerobic exercise training or to a control group. Polysomnography, with measurement of leg, thoracic and neck fluid volumes and upper-airway cross-sectional area (UA-XSA) before and after sleep, was performed at baseline and follow-up.17 patients per group completed the study. Apnoea–hypopnoea index decreased significantly more in the exercise group than in the control group (31.1±12.9 to 20.5±9.4versus28.1±13.5 to 27.0±15.1 events per h, p=0.047), in association with a greater reduction in the overnight change in leg fluid volume (579±222 to 466±163versus453±164 to 434±141 mL, p=0.04) and by a significantly greater increase in the overnight change in UA-XSA in the exercise group (p=0.04).In patients with CAD and sleep apnoea, exercise training decreases sleep apnoea severityviaattenuation of overnight fluid shift and an increase in UA-XSA.


2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Pradyumna Agasthi ◽  
Sivakanth Aloor ◽  
Avantika Chenna ◽  
Anekwe Onwuanyi

Background: Ghrelin (GH) is a gastrointestinal endocrine peptide regulating multiple biological processes including adipogenesis, glucose metabolism, cell differentiation and proliferation. Recent studies demonstrated that GH inhibits pro-atherogenic changes in vessel wall via inhibition of nuclear factor - B activity, a transcriptional factor mediating production pro-inflammatory cytokines and adhesion molecule expression in the endothelium. The aim of the current study is to conduct a meta-analysis to evaluate the relationship between serum GH levels and coronary artery disease (CAD). Methods: We searched MEDLINE, CINHAL and COCHRANE databases for studies reporting serum GH levels in the CAD and non CAD study population. We included case controls, cohort and cross-sectional studies. We calculated the weighted standardized mean difference (SMD) in serum GH levels between the CAD and control groups. Results: Our search strategy yielded 285 articles and we included 10 studies enrolling 1855 participants. The median age of the CAD group was 62 yrs. (IQR 60 - 63) compared to 61 yrs. (IQR 58 - 65) in the control group. The median body mass index in the CAD group was 28 kg/m2 (IQR 27.9 - 28) compared to 27 kg/m2 (IQR 26 - 27) in the control group. The unweighted median serum GH levels in the CAD group were 0.66 ng/ml (IQR 0.3 - 1.6) compared to 0.76 ng/ml (IQR 0.38 - 4.9) in the control group. The SMD of GH level was -0.44 (95% CI -0.56,-0.31) p<0.001 comparing those in the CAD group and control group. Conclusion: Serum GH levels are significantly and inversely associated with CAD. Current findings warrant the need to further investigate the role of GH in the pathogenesis of CAD.


Author(s):  
Chandan K. Jha ◽  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Naina Khullar ◽  
Suriya Rehman ◽  
...  

Aim: Studies have evaluated the association of miRNA-423 C>A genotyping with the susceptibility to various diseases such cancers, atherosclerosis and inflammatory bowel disease but the results were contradictory. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of coronary artery disease. MicroRNAs regulate expression of multiple genes involved in atherogenesis. Therefore, we investigated the association of microRNA-423C>T gene variations with susceptibility to coronary artery disease. Methodology: This study was conducted on 100 coronary artery disease patients and 117 matched healthy controls. The genotyping of the microRNA-423 rs6505162C>A was performed by using Amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution among the coronary artery disease cases and sex-matched healthy controls (P=0.048). The frequencies of all three genotypes CC, CA, AA reported in the patient’s samples were 55%, 41% and 4% and in the healthy controls samples were 55%, 41% and 4% respectively. Our findings showed that the microRNA-423 C>A variant was associated with an increased risk of coronary artery disease in codominant model (OR = 1.96, 95 % CI, 1.12-3.42; RR 1.35(1.05-1.75, p=0.017) of microRNA-423CA genotype and significant association in dominant model (OR 1.97, 95% CI (1.14-3.39), (CA+AA vs CC) and non-significant association for recessive model (OR=1.42, 95%CI=0.42-4.83, P=0.56, AA vs CC+CA).While, the A allele significantly increased the risk of coronary artery disease (OR =1.56, 95 % CI, 1.03-2.37; p=0.035) compared to C allele. Therefore, it was observed that more than 1.96, 1.97 and 1.56 fold increased risk of developing coronary artery disease. Conclusion: Our findings indicated that microRNA-423 CA genotype and A allele are associated with an increased susceptibility to Coronary artery disease.


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