The frequency of allelic polymorphism of genes encoding immunoproteasome catalytic subunits in acute coronary syndrome patients

Large multifunctional protease LMP2 (Arg60-->His) and LMP7 (Lys145-->Gln) gene allelic polymorphism in 200 patients with acute coronary syndrome and in 80 practically healthy people was determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphism is 52, 40.5 and 7.5 % correspondingly (in control group 53.8, 38.7, 7.5 %; P > 0.05 by chi2-test). Analysis of LMP7 gene polymorphism has shown that Lys/Lys - 89.5 %, Lys/Gln - 10.5 %, Gin/Gin - 0 % (in control group 93.8, 6.2, 0 % correspondingly; P > 0.05). The data show that LMP2 and LMP7 gene polymorphism is not a risk factor of acute coronary syndrome in Ukrainian population.     

Interleukin-8 gene polymorphism is associated with acute coronary syndrome in the Chinese Han population

Background

Acute coronary syndrome (ACS) is one of the most common forms of heart disease. Recent studies have shown that interleukin (IL)-8 plays a key role in the development of atherosclerotic plaques, but the relationship between the common genetic variants of IL-8 and ACS has not been extensively studied.

Methods

This case-control study in the Chinese Han population included 675 patients with ACS and 636 age- and sex-matched controls. We investigated IL-8 polymorphisms and their association with susceptibility to ACS. The investigation was replicated in the second study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.

Results

IL-8 −251 A/T polymorphism was associated with increased susceptibility to ACS (P = 0.004; odds ratio = 1.30; 95% confidence interval: 1.12–1.53). The second study yielded similar results. An increased IL-8 level was found in the plasma of acute myocardial infarction patients, suggesting that IL-8 −251 A/T may affect the expression of IL-8.

Conclusion

IL-8 −251 A/T polymorphism is associated with ACS risk in the Chinese Han population and the A allele of IL-8 −251 A/T may be an independent predictive factor for ACS.     

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome

Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions.Materials and methodsIn 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24 h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed >50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries.ResultsIn all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p < 0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p < 0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR = 1.155; 95%CI: 1.011; 1.32) (p < 0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR = 1.318, 95%CI: 1.097; 1.583) (p < 0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR = 0.152, 95%CI: 0.033; 0.695, p < 0.05).ConclusionsIn acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.     

Interleukin-1B (-511) gene polymorphism is associated with acute coronary syndrome in the Turkish population

Objectives: acute coronary syndrome (ACS) is defined as an inflammatory disease associated with development of atherosclerosis and instability. IL-1 is a candidate inflammatory cytokine that is thought to trigger ACS. The purpose of this study was to determine the relationship between IL-1 gene family polymorphisms (IL-1RN, IL-1B in positions -511 and +3953) and ACS in the Turkish population. Methods: a total of 381 people participated in the study, with 117 control subjects and 264 ACS patients. Of the 264 ACS patients, 112 were diagnosed with stable angina pectoris (SAP) and 152 were diagnosed with unstable angina pectoris (USAP). The polymerase chain reaction (PCR) was used to determine the genotype of IL-1RN. The genotypes of IL-1B (-511 and +3953) were determined by PCR, followed by restriction enzyme digestion of the PCR products. Results: there were no significant differences in both IL-1RN, IL-1B (-511 and +3953) genotype distributions and IL-1RN allele frequencies between ACS patients and the control subjects. In addition, no association was observed in the allele frequency of IL-1B (-511 and +3953) between ACS patients and controls (p = 0.113 and p = 0.859, respectively), or between SAP patients and controls (p = 0.575 and p = 0.359, respectively). However, IL-1B allele 1 (C) (-511) polymorphism in USAP patients was found to be significantly different from that of control subjects (p = 0.041, OR: 2.01; 95% CI: 1.985-3.933). A significant difference was also observed between USAP and SAP patients for IL-1B (+3953) allele 1 (C) polymorphism; (p = 0.043, OR: 1.522; 95% CI: 1.012-2.88). Conclusion: these results show that IL-1RN gene polymorphism has no association with ACS. However, the allele 1 (C) of IL-1B (-511) may be a risk factor for susceptibility to USAP in the Turkish population.     

The frequency of promoter polymorphism of the gene encoding epoxygenase 2J2 in patients with acute coronary syndrome

G⁻⁵⁰ → T promoter polymorphism of the gene encoding human epoxygenase 2J2 in 107 patients with acute coronary syndrome and in 104 healthy people was determined. It was shown that interrelation of genotypes G/G, G/T, and T/T was 91, 9, and 0%, respectively (in the control, 92, 7, and 1%; P > 0.05 by the χ² test). The data indicate that epoxygenase 2J2 gene polymorphism is not a risk factor of acute coronary syndrome in the population of the Ukraine.     

Lymphocyte DNA damage in patients with acute coronary syndrome and its relationship with severity of acute coronary syndrome

OBJECTIVE: The aim of this study was to investigate the association between lymphocyte DNA damage and acute coronary syndromes (ACS). METHODS: The study population contained 53 patients with ACS, 48 patients with stable angina and 35 voluntary healty subjects. DNA damage was assessed by alkaline comed assay in peripheral lymphocyte and plasma levels of total antioxidant capacity (TAC) were determined using a novel automated measurement method. RESULTS: In ACS patients, DNA damage was significantly higher than in patients with stable angina and control subjects (144+/-52 AU, 116+/-37, 68+/-34 AU; for three p<0.001, respectively). The TAC levels in patients with ACS were lower than the other groups (1.24+/-0.31 mmol Trolox equiv./l, 1.46+/-0.29 mmol Trolox equiv./l, p<0.05, respectively). DNA damage values in patients with acute miyocardial infarction were significantly higher than in patients with unstable angina (159.8+/-53.0 AU versus 131.8+/-48.4 AU; p<0.05, respectively). Lymphocyte DNA damage values in patients with ACS showed positive correlation with d-dimer (r=0.880, p<0.001) troponin I (r=538, p<0.001) and C-reactive protein (r=0.544, p<0.001) and negative correlation with TAC (r=-0.346, p=0.011). In multiple linear regression analysis, TAC (beta=-0.213, p=0.001) and d-dimer (beta=0.697, p<0.001) were independent predictors of DNA damage in patients with ACS. CONCLUSIONS:These findings indicate that lymphocyte DNA damage level increases in patients with ACS. Elevated DNA damage may be related with plaque instability and be useful for the identification of patients with acute coronary syndromes.     

NO Level and Endothelial NO Synthase Gene Polymorphism （Glu298Asp） in the Patients with Coronary Artery Disease from the Turkish Population

A healthy endothelium plays a core role in cardiovascu-lar control [1]. In the endothelial cell, nitric oxide (NO) issynthesized by the endothelial nitric oxide synthase (eNOS)encoded by a 26-exon gene (NOS 3) located on chromo-some 7 [2]. Besides its regulatory functions on vasomotortone and blood flow, endothelial NO is known to inhibitthe platelet activation and modulate migration and growthof the vascular smooth muscle [3]. Indirect evidence sug-gests that alterations of the NO pathwa…     

Frequency of the Pro 12Ala polymorphism of PPARgamma2 gene in Ukrainian population and its possible role in development of metabolic syndrome

Frequency of the Pro 12Ala gene polymorphism PPARg2 has been studied in 39 healthy men and 42 men with metabolic syndrome (MS) of the age of 40-65 years in Ukrainian population. The frequencies were 27.9% for 12Ala allele, 32.6% for Pro12Ala, and 4.4% for Ala1Ala that is close to the results of estimation of Czech population. The frequency of 12Ala allele was significantly less--18.4% (p < 0.05) in the persons with MS that corresponds to the pre-established information concerning the patients with diabetes of the 2nd type. A tendency has been detected to the increase of the body mass index in patients with 12Ala allele in the metabolic syndrome group.     

The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary syndrome in a Chinese case-control study

Numerous reports in the past few years have demonstrated that atherosclerosis is a lipid-driven, chronic inflammatory disease of the vessel. Recent studies have indicated that the immune mediator CD40-CD40L (CD40 ligand), which is expressed on several inflammatory cells within human atherosclerotic lesions, has roles in atherogenesis. A functional polymorphism (-1C>T, rs1883832) in the 5' untranslated region of TNFRSF5 gene has been reported to affect CD40 expression and be associated with several chronic inflammatory and autoimmune diseases. The aim of the present study was to validate the potential coronary artery disease susceptibility marker in a Chinese case-control study. A total of 160 patients with acute coronary syndrome (ACS) and 180 control subjects were used to genotype and identify this single-nucleotide polymorphism by polymerase chain reaction-restriction fragment length polymorphism and sequencing, respectively. Peripheral blood mononuclear cells were isolated and incubated with interferon-γ with or without pretreatment of fluvastatin, followed by measurement of CD40 expression using flow cytometry. In addition, soluble CD40L was determined by ELISA as another biomarker of coronary artery disease. The distribution of the rs1883832 genotypes (CC, CT, and TT) was 33.1%, 54.4%, and 12.5% in the ACS group and 22.8%, 53.3%, and 23.9% in controls, respectively. The frequency of the C allele was significantly higher among ACS patients compared with controls (60.3% vs. 49.4%, odds ratio=1.554, 95% confidence intervals: 1.146-2.107, p<0.05). ACS patients showed a significant increase of CD40 and sCD40L coexpression compared with controls (p<0.05). Cell culture experiments showed that CC carriers presented significantly higher CD40 expression levels than CT and TT subjects (p<0.05). Additionally, fluvastatin suppressed CD40 expression in all three genotypes. These data suggest that the single-nucleotide polymorphism of CD40 gene is associated with susceptibility to ACS in Chinese population, and the polymorphism may influence the CD40 production. These expand the understanding of inflammatory mechanisms during atherogenesis.     

Association of Klotho gene polymorphism with hypertension and coronary artery disease in an Iranian population

Background

Klotho, possibly an age-regulating protein, is considered an important factor contributing to the lifespan and pathophysiology of hypertension and coronary artery disease (CAD). The present study was carried out aiming to investigate the association of Klotho-rs564481 (C1818T) gene polymorphism with hypertension and CAD.

Methods

A total of 286 CAD-suspicious subjects were entered into this case-control study. The polymorphism was investigated in hypertensive patients with no CAD (H-Tens, n?=?60); hypertensive patients with CAD (CAD?+?H-Tens, n?=?95); CAD patients with no hypertension (CAD, n?=?61); and non-hypertensive non-CAD subjects, which were regarded as the control group (Ctrl, n?=?70). Genotype and allele frequencies were assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

A significant difference was found in allele frequency of Klotho C1818T among the four research groups (P?=?0.03). It was also found that wild-type homozygote subjects were negatively associated with hypertension as compared to heterozygote ones (OR?=?0.07 [95% CI: 0.008–0.69] P?=?0.02). Moreover, in the subgroups older than 57?years old, dominant genetic model demonstrated a negative association with CAD combined with hypertension (OR?=?0.31 [95% CI: 0.10–0.95] P?=?0.04).

Conclusions

In conclusion, Klotho C1818T variant may be associated with a decreased risk of hypertension. Moreover, aging enhanced positive effects of the Klotho polymorphism on CAD combined with hypertension, indicating the possibility that the KLOTHO gene might play a part in the age-related occurrence of CAD combined with hypertension.

     

Association of OX40 and OX40L gene polymorphisms with acute coronary syndrome in a Han Chinese population

OX40 and OX40L, members of the tumor necrosis factor receptor superfamily, are costimulatory molecules involved in the activation and proliferation of T lymphocytes. OX40L plays an important role in the process of atherosclerosis, and variants of OX40/OX40L are associated with myocardial infarction in European populations. Our study examined 235 patients with acute coronary syndrome (ACS) and 220 controls and sought to establish whether polymorphisms in OX40/OX40L are associated with atherosclerosis or myocardial infarction in the Han Chinese population. OX40 rs17568A/G, rs2298212A/G, and OX40L rs3850641A/G polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that carriers of the G allele of rs17568A/G had a significantly increased risk of ACS (p?=?0.023, adjusted odds ratio?=?1.72, 95% confidence interval?=?1.08-2.75) after adjusting for age, sex, diabetes, hypertension, and lipids. No significant association between rs2298212A/G or rs3850641A/G and the risk of ACS was found in this study. In conclusion, OX40 gene polymorphism may be associated with a risk of ACS in the Han Chinese population, although the association between OX40L polymorphisms and ACS requires further investigation.     

Primary percutaneous coronary angioplasty in patients with acute coronary syndrome and concomitant cancer

The paper gives the results of X-ray surgical treatment in patients with acute coronary syndrome who have been ascertained to have concomitant cancer during their examination. Cancer was found in 11 patients in their medical history and diagnosed in 2 patients during examination after surgical treatment and 1 patient one year after his hospital discharge. The results of combination treatment showed the high efficiency of X-ray surgical treatment for acute coronary syndrome. Recovery of TIMI-III blood flow through the infarct-related coronary artery was achieved in 100% of cases; immediate clinical efficiency was 97.4%. In the concomitant cancer group, the therapeutic efficacy was 100%; there were no complications during X-ray surgery. All the patients from this group were discharged from hospital in a satisfactory state to be followed up by a cardiologist and oncologist for further treatment. The study performed suggests that concomitant cancer is not a contraindication to primary coronary angioplasty in patients with acute coronary syndrome. Primary coronary angioplasty with stenting is a safe effective treatment for acute coronary syndrome in this category of patients.     

The role of polymorphic variants of gene of inducible NO-synthase NOS2 in brain infarction in patients with acute ischemic stroke

Cerebrovascular diseases including stroke are an important problem of public health. Stroke development depends on external factors and individual genetic specificity of patient. Excessive NO production by inducible NO-synthase (iNOS) damages brain tissue at various stages of the disease. The goal of this work was to study the role of 4 polymorphic variants of gene of inducible NO-synthase iNOS (-2447C/G, -1659C/T, -0,7(OTTA)n I/D, S608L (150C/T)) in brain infarction in patients with acute ischemic stroke. A statistically significant correlation between S608L (150C/T) polymorphism and infarction dynamics was observed during days 1-3 and 7-21 after infarction. These parameters correlated with neurological status estimated using the Orgogozo scale during days 1-7 of the disease development. It was demonstrated that genotype N150N was associated with ischemic focus propagation regardless of its volume and neurological status by Orgogozo scale in patients with acute stroke. It was also observed that genotype N150N had effect on ischemic damage during days 1-3 in case of low initial volume.     

Relationship between hemorheology and Glu(298)Asp polymorphism of endothelial nitric oxide synthase gene in patients with coronary artery disease

This study aimed to investigate the relationship between endothelial nitric oxide synthase Glu(298)Asp gene polymorphism and hemorheological parameters. Red blood cell (RBC) deformability, aggregation were measured using an ectacytometry, whole blood, plasma viscosities were determined by a viscometer. Restriction fragment length polymorphism was used to detect polymorphism. Plasma nitrite, nitrate concentrations were determined by Griess method. The genotype distribution of the control group was as follows: 50 (67.5%) GG, 21 (28.4%) GT, 3 (4.1%) TT. A 48 (57.8%) of the patients with CAD had GG, 28 (33.7%) GT, 7 (8.5%) of them TT genotype. RBC aggregation index of CAD patients with G allele was higher and t½ lower compared to controls carrying the same allele. The amplitude of RBC aggregation of healthy subjects with T allele, who are under increased cardiovascular risk was lower compared to control subjects with G allele. The results of this study indicate that, alterations in RBC aggregation seem to be a consequence of CAD, more than being a preexisting cause. Additionally, some compensatory mechanisms by causing decrements in RBC aggregation, may help regulation of circulation in healthy individuals with high cardiovascular risk.     

Identifying acute coronary syndrome patients approaching end-of-life

Background

Acute coronary syndrome (ACS) is common in patients approaching the end-of-life (EoL), but these patients rarely receive palliative care. We compared the utility of a palliative care prognostic tool (Gold Standards Framework (GSF)) and the Global Registry of Acute Coronary Events (GRACE) score, to help identify patients approaching EoL.

Methods and Findings

172 unselected consecutive patients with confirmed ACS admitted over an eight-week period were assessed using prognostic tools and followed up for 12 months. GSF criteria identified 40 (23%) patients suitable for EoL care while GRACE identified 32 (19%) patients with ≥10% risk of death within 6 months. Patients meeting GSF criteria were older (p = 0.006), had more comorbidities (1.6±0.7 vs. 1.2±0.9, p = 0.007), more frequent hospitalisations before (p = 0.001) and after (0.0001) their index admission, and were more likely to die during follow-up (GSF+ 20% vs GSF- 7%, p = 0.03). GRACE score was predictive of 12-month mortality (C-statistic 0.75) and this was improved by the addition of previous hospital admissions and previous history of stroke (C-statistic 0.88).

Conclusions

This study has highlighted a potentially large number of ACS patients eligible for EoL care. GSF or GRACE could be used in the hospital setting to help identify these patients. GSF identifies ACS patients with more comorbidity and at increased risk of hospital readmission.     

Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary syndrome

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30-50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31-2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23-2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.