C-reactive protein gene polymorphisms affect plasma CRP and homocysteine concentrations in subjects with and without angiographically confirmed coronary artery disease

Human C-reactive protein (CRP) is a reactant involved in the acute phase response and one of the many molecular factors involved in pathogenesis of coronary artery disease (CAD). CRP gene variants potentially mediate CRP plasma concentrations and the development of CAD. 220 Croatian subjects with angiographically confirmed CAD and 132 control subjects were included in the study. CRP gene polymorphisms 1059G/C and -717G/A were determined by RFLPs, using MaeIII and KspI endonuclease, respectively. Plasma concentrations of CRP and homocysteine were determined by immunoturbidimetry and FPIA, respectively. CRP 1059G/C gene variants were significantly associated with CAD (OR = 0.50; 95% CI = 0.27, 0.94; P = 0.032). Wild GG genotype and rare allele C carrier genotypes were 184 and 22 in CAD(+) group, and 101 and 24 in CAD(−) group, respectively. Multivariate analysis with age, gender, BMI, smoking status, hypertension and diabetes as covariates showed that 1059C carriers had lower CRP concentrations in CAD(−) (P = 0.010) and CAD(+) subjects (P = 0.028). This allele was also significantly associated with lower plasma homocysteine concentrations in both groups (P = 0.018 for CAD(−) and 0.002 for CAD(+). There was no significant difference between CAD(+) and CAD(−) subjects in absolute frequencies for CRP -717A/G gene variant, but multivariate analysis showed that carriers of the rarer G allele had significantly higher CRP plasma concentrations in CAD(−) subjects (P = 0.031) and higher homocysteine concentrations in CAD(+) group (P < 0.001). Atherosclerosis is an inflammatory disease resulting from different genetic and environmental factors. Results presented here support the contribution of CRP genetic variations in the development of CAD.     

Serum copper and zinc levels and copper/zinc ratio in patients with breast cancer

Serum copper, zinc levels, and the Cu/Zn ratio were evaluated in 31 patients with breast cancer and 35 healthy controls. Copper and zinc were determined by atomic absorbtion spectrophotometry. The mean serum copper level and the mean Cu/Zn ratio in patients with breast cancer were significantly higher than the control group (p<0.001 andp<0.001). In addition, the mean serum zinc level in patients with breast cancer was significantly lower than the control group (p<0.001). Neither serum copper and zinc levels nor the Cu/Zn ratio were of value in discriminating of the disease activity and severity. Interestingly, the Cu/Zn ratio in premenopausal patients was higher than postmenopausal patients (p<0.05) and this was not related to age. The further combined biological and epidemiological studies are necessary to investigate the roles of copper and zinc in breast cancer.     

Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease

The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.     

Serum copper levels and not zinc are positively associated with serum leptin concentrations in the healthy adult population

Leptin, the obesity gene protein product, is a hormone with multiple physiological functions in the human. However, there are few reports in the literature on its role in trace element metabolism in the normal population. Therefore, we investigated the association among serum leptin, zinc, copper, and zinc/copper ratio in 570 healthy men and women aged 15 yr and older. Serum leptin assay was done with a commercial enzymelinked immunosorbent assay kit; serum zinc and copper levels were measured by an atomic absorption spectrophotometer. Serum leptin was found to be positively associated with age (r=0.254, p<0.001), sex (r=0.406, p<0.001), body mass index (BMI) (r=0.553, p<0.001), and serum copper (r=0.419, p<0.001), but negatively associated with the zinc/copper ratio (r=−0.423, p<0.001). There was no significant association between serum leptin and zinc (r=−0.131, p>0.05). When the confounding effects of age, sex, and BMI were removed, serum leptin was still positively associated with serum copper (r=0.197, p=0.02) and the serum zinc/copper ratio (r=−0.182, p=0.03). These results suggest that copper and not zinc has an effect on serum leptin levels.     

Serum zinc and copper in patients with atherosclerosis andThromboangiitis obliterans

The serum concentration of Zn and Cu were determined in 126 controls and 160 patients with atherosclerosis obliterans (AO) and 53 patients with thromboangiitis obliterans (TO). The concentration of serum Zn decreases with age both in controls and patients with AO in all the evolutive stages of the disease. In patients with TO, the concentration of serum Zn shows no correlation with age. The significantly lower values of serum Zn in controls and patients with AO over 61 yr than those below this age is attributed to the decreased Zn supply, especially to some individual cellular abnormalities. The values of serum Cu are higher in patients with AO and TO than in controls irrespective of the evolutive stage of the disease. This was related to cigarette smoking and inflammation. The Zn/Cu ratio in the serum is below 1 in patients with AO and TO and in controls over 61-yr-old. The pathogenetic role of this ratio in atherosclerosis and inflammation still remains a controversial question.     

Serum concentrations of MCP-1 and IL-6 in combination predict the presence of coronary artery disease and mortality in subjects undergoing coronary angiography

The UBA–UBX domain-containing proteins can interact with ubiquitinated substrates and p97 during endoplasmic reticulum-associated degradation (ERAD). Here, we found that the expressions of all UBA–UBX genes p47, SAKS1, UBXD8, FAF1, and UBXD7 were elevated upon ER stress, albeit with different levels. Of which p47, SAKS1, and UBXD8 are ‘immediate’ respondents whereas FAF1 and UBXD7 were ‘late’ respondents to ER stress. Interestingly, the expression of specific UBA–UBX genes were altered in cells stably expressing three different ERAD substrates such as α-TCR, α1-antitrypsin, and δCD3. We first found that p47 and UBXD8 expression levels were increased in α-TCR and α1-antitrypsin stable cell lines, respectively, whereas SAKS1 expression level was reduced in all the three ERAD substrates tested. Of note, we also found p47 promotes, whereas SASK1 delays the degradation of a single ERAD substrate, α-TCR. Additionally, we found that SAKS1 selectively inhibits the degradation of ERAD substrates without affecting cytosolic proteasomal substrates. Taken together, our results identified that UBA–UBX proteins possess substrate selectivity and opposite role of two different UBA–UBX proteins in the degradation of a single ERAD substrate.     

Cholesterol-related gene variants are associated with diabetes in coronary artery disease patients

Molecular Biology Reports - Coronary artery disease (CAD) which is a complex cardiovascular disease is the leading cause of death worldwide. The changing prevalence of the disease in different...     

Serum omentin-1 levels are inversely associated with the presence and severity of coronary artery disease in patients with metabolic syndrome

Context: Omentin-1, an adipokine secreted from visceral adipose tissue, has been reported to be associated with coronary artery disease (CAD) and metabolic disorders.

Objective: To clarify the relationship between serum omentin-1 levels and the presence and severity of CAD in patients with metabolic syndrome (MetS).

Methods: We measured serum omentin-1 levels in 175 consecutive patients with MetS and in 46 controls.

Results: Serum omentin-1 levels are inversely associated with the presence and angiographic severity of CAD in MetS patients.

Conclusions: Serum omentin-1 might be a potential biomarker to predict the development and progression of CAD in MetS patients.     

Probing the epigenetic signatures in subjects with coronary artery disease

Depletion of S-adenosyl methionine and 5-methyltetrahydrofolate; and elevation of total plasma homocysteine were documented in CAD patients, which might modulate the gene-specific methylation status and alter their expression. In this study, we have aimed to delineate CAD-specific epigenetic signatures by investigating the methylation and expression of 11 candidate genes i.e. ABCG1, LIPC, PLTP, IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66 and TGFBR3. The methylation-specific PCR and qRT-PCR were used to assess the methylation status and the expression of candidate genes, respectively. CAD patients showed the upregulation of IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66, and TGFBR3. Hypomethylation of CDKN2A loci was shown to increase risk for CAD by 1.79-folds (95% CI 1.22–2.63). Classification and regression tree (CART) model of gene expression showed increased risk for CAD with F2RL3?>?3.4-fold, while demonstrating risk reduction with F2RL3?<?3.4-fold and IL-6?<?7.7-folds. This CAD prediction model showed the excellent sensitivity (0.98, 95% CI 0.88–1.00), specificity (0.91, 95% CI 0.86–0.92), positive predictive value (0.82, 95% CI 0.75–0.84), and negative predictive value (0.99, 95% CI 0.94–1.00) with an overall accuracy of 92.8% (95% CI 87.0–94.1%). Folate and B₁₂ deficiencies were observed in CAD cases, which were shown to contribute to hypomethylation and upregulation of the prime candidate genes i.e. CDKN2A and F2RL3. Early onset diabetes was associated with IL-6 and TNF-α hypomethylation and upregulation of CDKN2A. The expression of F2RL3 and IL-6 (or) hypomethylation status at CDKN2A locus are potential biomarkers in CAD risk prediction. Early epigenetic imprints of CAD were observed in early onset diabetes. Folate and B₁₂ deficiencies are the contributing factors to these changes in CAD-specific epigenetic signatures.

     

Super-ego in patients with coronary artery disease

In this paper, we explored the super-ego ofpatients with coronary artery disease. Research results have confirmed the initial hypothesis that a significant number of patients with coronary artery disease has rigorous super-ego. Among patients with coronary artery disease (N=50), and control group (N=50), we have found significant differences in the quality of super-ego and ego attitude towards the demands of the super-ego. The results of this research contribute to understanding the impact of psychological factors in coronary artery disease.     

Analysis of serum copper and zinc concentrations in cancer patients

Several studies have shown that plasma copper concentrations are increased in various carcinomas. Zinc acts as a cellular growth protector, including growth of neoplastic cells, and its deficiency was demonstrated to be involved in several stages of malignant transformation. However, the usefulness of the serum zinc and copper determinations in cancer prevention, detection, monitoring treatment, and prognosis requires further investigations. The aim of the present study was to compare the serum copper and zinc levels in patients with cancer of the lung (PC), breast (BC), gastrointestinal tract (GIC), and gynecological (GYNC) malignancy with progress of the disease. The results of the study have shown a significant increase in the mean total serum Cu levels and the serum Cu/Zn ratio in all patient groups with cancer compared to a control group. Increased mean serum concentrations and Cu/Zn ratios were found in the whole group (ALLC), and for the GIC and GYNC groups with local as well as metastasized (Meta) disease in comparison with the control group. The mean serum concentrations of Zn were decreased only in metastasized ALLC and GYNC groups.     

Circulating growth hormone releasing factor concentrations in normal subjects and patients with acromegaly.

A highly specific and sensitive radioimmunoassay was developed for measuring circulating growth hormone releasing factor (GRF) in human plasma. Before measuring immunoreactive GRF plasma samples were extracted on to Vycor glass. Immunoreactive GRF concentrations in plasma samples from 37 fasting normal subjects ranged from less than 10 to 60 ng/l (mean 21 ng/l). Fasting concentrations in 76 out of 80 acromegalic subjects were within the normal range, but the remaining four patients had values of 92 to 25 000 ng/l. Of these, only the patient with the highest concentration had evidence of ectopic GRF secretion from a disseminated carcinoid tumour. Two of the others had longstanding pituitary tumours, and the fourth patient had a pituitary growth hormone (GH) secreting tumour proved by its removal and subsequent remission of acromegaly. There was no correlation between serum GH and plasma immunoreactive GRF concentrations, irrespective of whether the patients were untreated or had been given radiotherapy or dopamine agonists. The assay should help elucidate the physiological role(s) of GRF and may also prove useful in differentiating between pituitary and hypothalamic defects in patients with acromegaly.     

Relation between zinc, copper, and magnesium concentrations following cardiopulmonary bypass and postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting

Atrial fibrillation is the most frequently encountered arrhythmia following cardiac surgery. Since the essential trace elements zinc, copper, and magnesium are suspected to have an effect on postoperative atrial fibrillation, the concentrations of these elements were determined by flame atomic absorption spectrophotometry in the plasma of 60 patients undergoing elective coronary artery bypass grafting. Blood samples were collected every 30 min during cardiopulmonary bypass and postoperatively. Plasma concentrations of copper, zinc, and magnesium were measured with flame atomic absorption spectrophotometry. All patients were monitored by continuous electrocardiography until they became outpatients or immediately after atrial fibrillation had taken place. Atrial fibrillation occurred in 13 of the 60 patients, corresponding to 21.7%. The zinc and copper concentrations at postoperative days 1 and 3 were significantly different (P < 0.05) between patients with and without atrial fibrillation. The concentrations of zinc following cardiopulmonary bypass recovered more slowly in patients with postoperative atrial fibrillation than in patients without it. Whether or not supplemental zinc could lower the incidence of postoperative atrial fibrillation should be evaluated in future prospective randomized clinical trials.     

Presence and extent of cardiac computed tomography angiography defined coronary artery disease in patients presenting with syncope

Background

In syncope patients, presence of coronary artery disease (CAD) is associated with poor prognosis. However, data concerning CAD prevalence in syncope patients without known cardiovascular disease are lacking. Therefore, the aim of this study was to investigate presence and extent of CAD in syncope patients.

Methods

We included 142 consecutive patients presenting with syncope at the outpatient cardiology clinic who underwent coronary computed tomography (CT) angiography. Syncope type was ascertained by two reviewers, blinded for coronary CT angiography results. Of the patients, 49 had cardiac syncope (arrhythmia or structural cardiopulmonary disease) and 93 had non-cardiac syncope (reflex [neurally-mediated], orthostatic or of unknown cause). Cardiac syncope patients were compared with matched stable chest pain patients regarding age, gender, smoking status, diabetes mellitus type 2 and systolic blood pressure.

Results

Distribution of CAD presence and extent in cardiac and non-cardiac syncope patients was as follows: 72% versus 48% any CAD; 31% versus 26% mild, 8% versus 14% moderate and 33% versus 7% severe CAD.Compared with non-cardiac syncope, patients with cardiac syncope had a significantly higher CAD presence and extent (p = 0.001). Coronary calcium score, segment involvement and stenosis score were also higher in cardiac syncope patients (p-values ≤0.004). Compared to the chest pain control group, patients with cardiac syncope showed a higher, however, non-significant, prevalence of any CAD (72% versus 63%) and severe CAD (33% versus 19%).

Conclusion

Patients with cardiac syncope show a high presence and extent of CAD in contrast to non-cardiac syncope patients. These results suggest that CAD may play an important role in the occurrence of cardiac syncope.

     

High serum interleukin-18 concentrations in patients with coronary artery disease and type 2 diabetes mellitus

AIMS: The aim of our study was to analyse the serum level of interleukin 18 (IL-18) in coronary artery disease (CAD) patients with type 2 diabetes mellitus (DM), and to relate this to clinical findings. METHODS: The IL-18 level was measured by ELISA in serum samples from 130 CAD patients prior to their first, elective, coronary artery bypass surgery. Forty-three of them had been diabetic for several years. A control group consisted of 31 healthy people matched according to age, BMI, lipid and smoking status. RESULTS: The CAD patients with DM were similar to the non-diabetic CAD patients with respect to age, BMI, grade of heart failure, ejection fraction. There were no differences in the duration of CAD, history of myocardial infarction and PTCA or instability of angina. The serum level of IL-18 was higher in the CAD patients than in the control group. The CAD patients with DM had a higher concentration of IL-18 compared to the non-diabetic CAD group. The diabetic patients with triple-vessel disease were characterized by a higher concentration of IL-18 than the non-diabetic patients with the same grade of CAD. Smoking affected the IL-18 concentration, particularly in the diabetic patients. CONCLUSION: Type 2 DM predisposes patients, especially those with multi-vessel CAD who were smokers, to a higher serum level of IL-18, which may help explain their vulnerability to fatal, secondary cardiovascular events. These patients should be in the first line for stringent, secondary cardiovascular prevention.     

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.