INVESTIGATION OF RELATIONSHIP BETWEEN rs1800796 VARIANTS OF INTERLEUKINE-6 GENE AND CORONARY ARTERY DISEASE

Purpose The goals of the present study were to assess the genotypic and allelic distribution of Bsm-I (rs1544410) and Apa-I (rs7975232) polymorphisms of the vitamin D receptor (VDR) gene in coronary artery disease (CAD) patients in comparison to control patients of the same age without CAD and to determine whether these gene variants are associated with dyslipidemia. Materials and Methods Based on a case-control design, 302 hospitalized patients with CAD and 194 people of comparable age without CAD were enrolled in the study. The BsmI and ApaI polymorphisms of VDR gene were studied using polymerase chain reaction followed by restriction analysis. The allele digested by the restriction enzyme was denoted by a lower letter, whereas that not digested was indicated by a capital letter. Determination of the level of vitamin D and immunoreactive insulin in the blood serum was carried out using the immuno-enzyme method. Results The bb genotype of Bsm-I VDR gene polymorphism was detected more often in patients with CAD than in the comparison group with an increased risk of CAD by 1.52 times (p=0.006, OR=1.52(1.05÷2.2). The level of HDL cholesterol was higher in CAD patients − carriers of BB genotype compared to its level in Bb genotype carriers and bb genotype carriers (1,13±0,05 mmol/l, 1,01±0,03 mmol/l, 1,02±0,03 mmol/l respectively, p<0,05). The level of vitamin D was higher in patients with BB genotype compared to its level in bb genotype carriers (45.12±3.73 nmol / l and 34.16±1.95 nmol/l respectively, p=0.008). The occurrence of a allele of Apa-I VDR gene polymorphism was higher in patients with CAD than in the control group (p=0.02, OR=1.21(0.93÷1.57). HDL cholesterol level was higher in CAD patients - AA genotype carriers compared with carriers of Aa and aa genotypes (1.18±0.08 mmol / l, 1,02±0.02 mmol / l and 1.01±0.03 mmol/l respectively, p<0,05). Immunoreactive insulin level was significantly higher in CAD patients – aa genotype carriers. No differences in LDL cholesterol and triglycerides were found. Vitamin D level was lower in CAD patients - Aa and aa genotype carriers (33,8±33,9 nmol/l ,p=0,02 and 24,7±4,9 nmol/l, p=0,05 respectively in comparison to vitamin D level = 43,3 ±4,2 nmol/l in AA genotype carriers). Conclusion The bb genotype of Bsm-I VDR gene polymorphism is associated with an increased risk of CAD. A carriage of b allele in CAD patients is associated with lower level of vitamin D and HDL cholesterol. A carriage of a allele of Apa-I VDR gene polymorphism in CAD patients is associated with lower level of vitamin D and HDL cholesterol.

Genetic polymorphisms in glutathione S-transferase (GST) genes may modulate the risk of cardiovascular diseases. The objective of present study was to investigate the potential association between the polymorphisms of GSTM1/T1 and P1 genes and their influence on diverse clinical parameters and oxidative stress biomarkers in coronary artery disease (CAD) patients in Asian Indians. The present study includes 562 angiographically confirmed CAD patients and 564 healthy control subjects from the north Indian population. Anthropometric and clinical measurements were performed for all the participants. The oxidative stress biomarkers including malondialdehyde and total antioxidant capacity were also measured. The genotyping of the GSTM1/T1 and P1 genes was performed using the multiplex-PCR and PCR-RFLP methods. The CAD patients exhibit significantly high values of waist circumference, waist-to-hip ratio, body fat (%), glucose, triglycerides, and very low-density lipoprotein, and reduced high-density lipoprotein levels compared to control subjects (P<0.001). Malondialdehyde levels were significantly enhanced, and the total antioxidant capacity was reduced in CAD patients compared to controls (P<0.001). However, no significant difference in body mass index and total cholesterol levels were observed in CAD patients and control subjects. The frequencies of the GSTM1 and GSTM1/T1 null genotypes in the CAD patients were significantly higher than the control subjects. In contrast, the GSTT1(-) genotype frequencies were significantly lower in CAD patients than the controls. Logistic regression analysis of the data revealed the null genotype of GSTM1 and the GG genotype of the GSTP1 (313A/G) gene were associated with an approximately twofold enhanced risk of developing CAD, whereas GSTT1(-) plays a defensive role against CAD development in north Indians. Upon stratification of data according to the genotypes of the GSTM1/T1 and P1 genes, we did not find significant a difference among the various metabolic traits in CAD patients and controls. Our results suggest that oxidative damage induced by lipid peroxidation with reduced antioxidant capacity and genetic variants in GST genes (GSTM1/T1 and P1) may modify the risk of CAD development in Asian Indian population.

BackgroundIt is known that patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are characterized with a variability of traditional and non-traditional cardiovascular risk factors for the early development...

CAD increases the long noncoding RNA PUNISHER in small extracellular vesicles and regulates endothelial cell function via vesicular shuttling

Apolipoprotein C-III (apoC-III) is a marker of triglyceride (TG)-rich lipoproteins, which are often increased in metabolic syndrome (MS). The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apoC-III levels. To evaluate the contribution of apoC-III levels and T-455C polymorphisms in the coronary artery disease (CAD) risk of MS patients, we studied 873 patients, 549 with CAD and 251 with normal coronary arteries. Patients were classified also as having or not having MS (MS, n = 270; MS-free, n = 603). Lipids, insulin, apolipoprotein levels, and APOC3 T-455C genotypes were evaluated. ApoC-III levels were significantly increased in MS patients, and the probability of having MS was correlated with increasing quartiles of apoC-III levels. MS patients with CAD had significantly higher apoC-III levels than did CAD-free MS patients. The carriership for the -455C variant multiplied the probability of CAD in MS in an allele-specific way and was associated with increased apoC-III and TG levels. Obesity was less frequent in MS carriers of the -455C allele than in MS noncarriers (21.6% vs. 34.8%, P < 0.05). In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents.

Coronary artery disease (CAD) is a common health problem with a high rate of disability and death. Dyslipidemia and altered metabolism of Apo-lipoproteins are involved in the CAD pathogenesis. The current study investigated two common polymorphisms (rs429358 and rs7412) and promoter DNA methylation status of APOE in the Iranian CAD patients and control subjects. Two hundred angiographically documented CAD patients and 200 control subjects were included in the study. The APOE polymorphism analysis was done by PCR-RFLP technique and DNA methylation status was evaluated by methylation specific PCR. The assay of lipid levels was conducted using standard colorimetric protocols. Results indicated that the frequency of ε3/ε4 and ε2/ε3 genotypes was significantly more common in CAD group compared with control group. Relative to wild type genotype (ε3/ε3), CAD patients with ε3/ε4 and ε2/ε3 genotypes displayed significantly higher concentration of total-cholesterol and LDL-cholesterol. The frequency of DNA methylation of APOE was similar between the two studied groups. However, the methylation frequency of APOE gene was significantly higher in triple stenotic vessels relative to single stenotic vessels (P=0.032). In conclusion The present study indicated that the rs429358 and rs7412 polymorphisms are significantly risk factors for development and severity of CAD. Also, APOE methylation status may be involved in the severity but not in the development of CAD.

Objectives: Coronary artery disease (CAD) is the leading cause of disability and global death. Homocysteine is a major risk factor for CAD. High plasma homocysteine levels are an independent risk factor for this disease. Methylenetetrahydrofolate reductase (MTHFR) is one of the essential enzymes of homocysteine metabolism. In this way, mutations of genes encoding enzyme reduce its activity, which can increase blood homocysteine levels and ultimately raise the risk of CAD. Accordingly, this study aimed to investigate the association between MTHFR C677T polymorphism and homocysteine with CAD disease. Materials and Methods: The present investigation is a case-control study conducted on the patients of Heshmat hospital, Rasht, Iran. The demographic characteristics of 90 patients and 76 controls were obtained by questionnaires and blood samples were collected to evaluate homocysteine levels and gene polymorphism. MTHFR C677T polymorphism and blood homocysteine levels were assessed using amplification refractory mutation system polymerase chain reaction (ARMS-PCR) and ELISA, respectively, and a comparison was made between the two groups. The statistical analysis of the data was performed using SPSS software, version 21. Results: The frequency of C677T polymorphism genotypes in the control and patient groups was not statistically significant (P = 0.384). The highest frequency of genotype in the control (46.1%) and patient (50%) groups was shown in CT. Plasma homocysteine levels were significantly higher in CAD patients than in the control group (P = 0.001). Conclusion: The results of this study showed that the TT genotype of C677T polymorphism has a protective effect on CAD. Although the results obtained for C677T polymorphism are not statistically significant, this genotype had little effect on atherosclerosis. Consequently, the interaction of MTHFR gene polymorphism with CAD may be due to C677T genotype and homocysteine levels in the selected population of Guilan.

ObjectiveIn this study, we evaluated obesity as a single risk factor for coronary artery disease (CAD), along with the synergistic effect of obesity and other risk factors.MethodsA retrospective study of 7,567 patients admitted to hospital for chest pain from 2005 to 2014 and underwent cardiac catheterization. Patients were divided into two groups: obese and normal with body mass index (BMI) calculated as ≥30 kg/m2 and <25, respectively. We assessed the modifiable and non-modifiable risk factors in obese patients and the degree of CAD.ResultsOf the 7,567 patients who underwent cardiac catheterization, 414 (5.5%) had a BMI ≥30. Of 414 obese patients, 332 (80%) had evidence of CAD. Obese patients displayed evidence of CAD at the age of 57 versus 63.3 in non-obese patients (p<0.001). Of the 332 patients with CAD and obesity, 55.4% had obstructive CAD versus 44.6% with non-obstructive CAD. In obese patients with CAD, male gender and history of smoking were major risk factors for development of obstructive CAD (p=0.001 and 0.01, respectively) while dyslipidemia was a major risk factor for non-obstructive CAD (p=0.01). Additionally, obese patients with more than one risk factor developed obstructive CAD compared to non-obstructive CAD (p=0.003).ConclusionHaving a BMI ≥30 appears to be a risk factor for early development of CAD. Severity of CAD in obese patients is depicted on non-modifiable and modifiable risk factors such as the male gender and smoking or greater than one risk factor, respectively.

Background: Coronary Artery Disease (CAD) is a major cause of mortality in most countries. Many risk factors such as high blood pressure, hyperlipidemia, diabetes, age, sex, obesity, smoking, and family history play a role in CAD. The aim of this study was to evaluate the concentration of Total Sialic Acid (TSA) and Lipid Profiles (LP) with the Severity of the Vessel in patients with non-smoker and diabetic CAD, so that by measuring these parameters, effective help for diagnosis and prevention for healthy people Prone to CAD, and also control the treatment of patients. Methods: In this study, 200 individual including 160 patient and 40 control group were considered. All patient groups were non-smokers and diabetic. Patients were divided into 4 groups according to the results of angiography: Patients with Normal angiography (n = 40) with one eclipse (n = 40), patients with double stenosis (n = 40) and patients with eclipse Three vessels (n = 40). The control group was chosen from people who had no history of CAD and other diseases. The lipid profile was measured by standard methods and serum total sialic acid was measured by ELISA method. Results: There was no significant difference between the two groups in age and sex, but there was a significant difference in family history (p&lt;0.05). There was a significant difference in serum glucose level between the patient and the control group (p&lt;0.05), Also hs-CRP serum levels were normal in two patient and control groups. Serum levels of cholesterol, triglyceride and LDL in patient group were significantly higher than that of the control group but HDL serum level was adverse (p &lt;0.05), Also TSA serum level in the patient group was significantly higher than the control group (p&lt;0.05). Conclusion: Serum Total Sialic Acid level in non-smoker and diabetic CAD patients has a significant increase compared to the control group. It seems that the above biochemical parameters contribute significantly to the development and progression of atherosclerosis and CAD, by which timely measurements of these parameters in healthy individual probably can be helpful in preventing and improving CAD and controlling the treatment of patients.

Background: Coronary Artery Disease (CAD) is a major cause of mortality in most countries. Many risk factors such as high blood pressure, hyperlipidemia, diabetes, age, sex, obesity, smoking, and family history play a role in CAD. The aim of this study was to evaluate the concentration of Total Sialic Acid (TSA) and Lipid Profiles (LP) with the Severity of the Vessel in patients with non-smoker and diabetic CAD, so that by measuring these parameters, effective help for diagnosis and prevention for healthy people Prone to CAD, and also control the treatment of patients. Methods: In this study, 200 individual including 160 patient and 40 control group were considered. All patient groups were non-smokers and diabetic. Patients were divided into 4 groups according to the results of angiography: Patients with Normal angiography (n = 40) with one eclipse (n = 40), patients with double stenosis (n = 40) and patients with eclipse Three vessels (n = 40). The control group was chosen from people who had no history of CAD and other diseases. The lipid profile was measured by standard methods and serum total sialic acid was measured by ELISA method. Results: There was no significant difference between the two groups in age and sex, but there was a significant difference in family history (p<0.05). There was a significant difference in serum glucose level between the patient and the control group (p<0.05), Also hs-CRP serum levels were normal in two patient and control groups. Serum levels of cholesterol, triglyceride and LDL in patient group were significantly higher than that of the control group but HDL serum level was adverse (p <0.05), Also TSA serum level in the patient group was significantly higher than the control group (p<0.05). Conclusion: Serum Total Sialic Acid level in non-smoker and diabetic CAD patients has a significant increase compared to the control group. It seems that the above biochemical parameters contribute significantly to the development and progression of atherosclerosis and CAD, by which timely measurements of these parameters in healthy individual probably can be helpful in preventing and improving CAD and controlling the treatment of patients.

Coronary artery disease (CAD) is one of the cardiovascular diseases, which is caused by a reduced amount of oxygen and blood that goes to the heart. CAD includes stable angina, unstable angina, myocardial infarction, and sudden cardiac death. It is a common cause of death in both men and women. The environmental and genetic factors are involved in the development of CAD. Multiple gene polymorphisms are risk factors of CAD. To evaluate the association between EL 584C/T polymorphism, CAD risk, and lipid profile in an Egyptian population. This is a case-control study. The patients were classified into three groups: Group A: Control group, this group included 42 apparently healthy people. Group B: included 42 subjects diagnosed with previous myocardial infarction (MI). Group C: included 42 subjects diagnosed with unstable angina (UA). The frequencies of TT and CT genotypes and T allele were higher in control healthy individuals than CAD patients. In addition, the risk of CAD was significantly lower in individuals carrying T allele (P = 0.001). Serum high-density lipoprotein (HDL) levels were significantly higher in healthy individuals and CAD patients (MI and UA patients) carrying EL 584 T allele compared with those carrying CC genotype (P ≤ 0.001). By multiple logistic regression, we found that the protective effect of T allele remained significant (P = 0.005) and it decreased the risk of CAD independent of plasma HDL levels. There was a significant difference between 584C/T polymorphism in the EL gene and CAD and HDL level. T-allele carriers had a higher HDL level and were protected from CAD. T allele was significantly associated with the decreased risk of CAD independent of plasma HDL levels.

BACKGROUND AND OBJECTIVESUnderstanding the nature and pattern of young coronary artery disease (CAD) is important due to the tremendous impact on these patients’ socio-economic and physical aspect. Data on young CAD in the southeast Asian region is rather patchy and limited. Hence we utilized our National Cardiovascular Disease Database (NCVD)—Percutaneous Coronary Intervention (PCI) Registry to analyze young patients who underwent PCI in the year 2007 to 2009.DESIGN AND SETTINGSThis is a retrospective study of all patients who had undergone coronary angioplasty from 2007 to 2009 in 11 hospitals across Malaysia.METHODSData were obtained from the NCVD—PCI Registry, 2007 to 2009. Patients were categorized into 2 groups—young and old, where young was defined as less than 45 years for men and less than 55 years for women and old was defined as more than or equals to 45 years for men and more than or equals to 55 years for women. Patients’ baseline characteristics, risk factor profile, extent of coronary disease and outcome on discharge, and 30-day and 1-year follow-up were compared between the 2 groups.RESULTSWe analyzed 10 268 patients, and the prevalence of young CAD was 16% (1595 patients). There was a significantly low prevalence of Chinese patients compared to other major ethnic groups. Active smoking (30.2% vs 17.7%) and obesity (20.9% vs 17.3%) were the 2 risk factors more associated with young CAD. There is a preponderance toward single vessel disease in the young CAD group, and they had a favorable clinical outcome in terms of all-cause mortality at discharge (RR 0.49 [CI 0.26–0.94]) and 1-year follow-up (RR 0.47 [CI 0.19–1.15]).CONCLUSIONWe observed distinctive features of young CAD that would serve as a framework in the primary and secondary prevention of the early onset CAD.

Hypercholesterolaemia (HC) impairs arteriogenesis, i.e. collateral artery growth. Monocytes are crucial mediators of arteriogenesis. We investigated the impact of the cardiovascular risk factor HC on ligand-induced monocyte chemotaxis. The migratory response of monocytes towards the arteriogenic ligands vascular endothelial growth factor-A (VEGF-A) and monocyte chemoattractant protein-1 (MCP-1) in hypercholesterolaemic coronary artery disease (CAD) patients (n = 14), hypercholesterolaemic controls (n = 8) and age-matched healthy controls (n = 19) was analysed. Furthermore, the serum VEGF-A level was determined in all individuals. VEGF-A-induced monocyte chemotaxis was severely impaired in hypercholesterolaemic CAD patients when compared with age-matched healthy controls (P < 0.001). The same was true for the migratory response towards MCP-1 (P < 0.001). VEGF-A- and MCP-1-induced monocyte chemotaxis of hypercholesterolaemic controls was also decreased in comparison with the healthy control group, but not as severe as observed in the hypercholesterolaemic CAD patients. VEGF-A serum levels did not differ between the three study groups. Hypercholesterolaemia severely impairs monocyte function in hypercholesterolaemic CAD patients. Monocyte dysfunction is probably connected to impaired collateral artery growth. The duration of the cardiovascular risk factor HC seems to influence the extent of monocyte dysfunction, as there exists a continuum of diminished monocyte chemotaxis in the three study groups. Further trials are warranted in order to determine whether statins can reverse the negative influence of HC on cell function.

Chemokine receptor 5 (CCR5) deletion polymorphism in North Indian patients with coronary artery disease

BackgroundThere is growing evidence that Chlamydia pneumoniae may be involved in the pathogenesis of atherosclerosis, as several studies have demonstrated the presence of the organism in atherosclerotic lesions. C. pneumoniae infections, which are especially persistent infections, have been difficult to diagnose either by serological methods or isolation of the organism from the tissue. Nucleic Acid Amplification tests (NAATs) has emerged as an important method for detecting C. pneumoniae. Inspite of high prevalence of C. pneumoniae specific antibodies in coronary heart disease patients, direct detection of C. pneumoniae in circulating blood of coronary artery disease (CAD) patients by sensitive nucleic acid amplification tests nested PCR (nPCR), multiplex PCR (mPCR) has not been carried out is required. Further correlation of the presence of C. pneumoniae in blood of CAD patients with C. pneumoniae specific IgA and IgG antibodies, which may indicative of the status of infection with the progression of atherosclerosis. This will help in order to prepare strategies for the antibiotic intervention to avoid the progression towards CAD.MethodsVenous blood was obtained from 91 CAD patients and 46 healthy controls. Nucleic acid amplification tests viz. nested -, semi-nested – and multiplex PCR were used for detection of C. pneumoniae. ELISA carried out prevalence of C. pneumoniae specific IgG and IgA antibodies.Results29.67% (27/91) patients were positive for C. pneumoniae using nested PCR. The sensitivity and specificity of semi-nested and multiplex PCR were 37.03%, 96.96% and 22.22%, 100% with respect to nested PCR. Positive nPCR patients were compared with presence of C. pneumoniae specific IgA, IgA+IgG and IgG antibodies. Among 27 (29.67%) nPCR C. pneumoniae positive CAD patients, 11(12%) were IgA positive, 13(14.2%) were IgA+IgG positive and only1 (1.1%) was IgG positive. A significant presence of C. pneumoniae was detected in heavy smokers, non-alcoholics and with family histories of diabetes and blood pressure group of CAD patients by nPCR.ConclusionThe results indicate synergistic association of C. pneumoniae infection and development of CAD with other risk factors. We also detected increased positivity for C. pneumoniae IgA than IgG in nPCR positive CAD patients. Positive nPCR findings in conjunction with persisting high C. pneumoniae specific antibody strongly suggest an ongoing infection.