OBJECTIVETo assess the association between single nucleotide polymorphism rs501120 and progress of unstable coronary atherosclerotic plaque in diabetes mellitus complicated with acute coronary syndrome (ACS).

METHODSNine hundred and two patients with diabetes complicated with acute coronary syndrome were enrolled. The genotype of rs501120 was determined with TaqMan-MGB probes. Two hundred and five cases of TT genotype, 205 age-and sex-frequency-matched cases of TC genotype and 205 age- and sex-frequency-matched cases of CC genotype were chosen and followed up for 3 years. Clinical data and re-occurrences of ACS were recorded.

RESULTSPatients with TT genotype had a significantly higher incidence of recurrence of ACS than those with CC genotype (TT vs. CC: OR 1.7, 95%CI 1.1-2.7, P= 0.02). And the significance has remained even after adjusting for conventional risk factors by logistic regression (OR 1.6, 95% CI1.05-3.6, P= 0.03). Patients with TT genotype had a significantly higher incidence of myocardial infarction than those with CC genotype(TT vs. CC: OR 1.9, 95% CI 1.2-3.2, P= 0.007).

CONCLUSIONOur results has suggested an association between the rs501120 polymorphism and progress of unstable coronary atherosclerotic plaque.

Acute Coronary Syndrome ; genetics ; Aged ; Coronary Artery Disease ; genetics ; Diabetes Complications ; genetics ; Disease Progression ; Female ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Plaque, Atherosclerotic ; genetics

BACKGROUNDScavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 (SR-PSOX/CXCL16) promotes foam cell formation through the tumor necrosis factor (TNF)-alpha mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell (SMC) proliferation, we presume that the monocyte SR-PSOX/CXCL16 detection in the patients' peripheral blood will be important for early diagnosis and prognosis of atherosclerosis (AS).

METHODSEnrolled in this study were 40 patients with acute coronary syndrome (ACS), including 20 patients with acute myocardial infarction (AMI) and 20 patients with unstable angina pectoris (UAP), and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR), with beta-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR-PSOX was analyzed with a confocal microscope.

RESULTSThe expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls (P < 0.05); however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group (P > 0.05). Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was proportionate to the degree of inflammation in the portal hepatis and folia.

CONCLUSIONSThe expression of CXCL16/SR-PSOX in the monocytes of peripheral blood was significantly higher in ACS patients than in the controls. CXCL16/SR-PSOX-mediated inflammation may contribute to the pathogenesis of ACS, and CXCL16 may play an important role in the pathogenesis and development of AS in humans.

Acute Coronary Syndrome ; immunology ; Blotting, Western ; Chemokine CXCL16 ; Chemokines, CXC ; blood ; genetics ; Coronary Angiography ; Fluorescent Antibody Technique ; Humans ; RNA, Messenger ; blood ; Receptors, Scavenger ; blood ; genetics

Objective: To investigate the effects of clopidogrel resistence and CYP2C19 genotype on the clinical prognosis of acute coronary syndrome(ACS) patients undergoing percutaneous coronary intervention(PCI). Methods: This study was a retrospective cohort study. ACS patients who underwent PCI in Beijing Anzhen Hospital from October 2015 to January 2017 were recruited. The inhibition rate of adenosine diphosphate(ADP) was monitored by thromboelastography. All of these patients were divided into clopidogrel resistance and non-resistance group according to the monitoring results. CYP2C19 genotype was detected by TaqMan probe-based real-time quantitative PCR. Patients were divided into slow, medium and fast metabolic group, according to the CYP2C19 genotype. After 12 months of follow-up, the end points included all-cause death, cardiac death, angina, myocardial infarction, stent thrombosis, ischemic stroke and hemorrhage were collected. Combined thrombotic events were defined as a composite of angina, myocardial infarction, stent thrombosis and ischemic stroke. The differences of the incidence of clinical events between groups were compared. Cox regression was used to analyze the effects of clopidogrel resistance and CYP2C19 genotype on the combined thrombotic events, cardiac death and hemorrhage. Results: A total of 1 696 patients were included, and the age was (59.4±9.6) years, with 1 280(75.5%) males. There were 471 cases(27.8%) in clopidogrel resistance group, and 1 225 cases(72.2%) in clopidogrel non-resistance group. There were 218 patients(12.9%) were in slow metabolic group, 668(39.4%) in medium metabolic group, and 810 (47.8%) in fast metabolic group. The median follow-up time was 13.3 months, and 131 cases were lost to follow-up, with a loss follow-up rate of 7.7%. Compared with the clopidogrel non-resistance group, the clopidogrel resistance group had a higher incidence of myocardial infarction(7.6%(36/471) vs. 5.1%(62/1 225), P=0.041), a lower incidence of hemorrhage (13.2%(62/471) vs. 17.9%(219/1 225), P=0.020) and minor hemorrhage(11.5%(54/471) vs. 15.8% (194/1 225), P=0.022). There were no statistically significant difference in all-cause death, cardiac death, angina, stent thrombosis, ischemic stroke and severe bleeding between clopidogrel resistance and non-resistance group(all P>0.05). There was no statistically significant difference in the incidence of endpoint events among different CYP2C19 genotypes (all P>0.05). Cox regression analysis showed that clopidogrel resistance was an independent factor of combined thrombotic events (OR=2.334, 95%CI 1.215-4.443, P=0.016) and bleeding events (OR=0.481, 95%CI 0.174-0.901, P=0.023). While CYP2C19 genotype was not independent factor for combined thrombotic events, cardiac death and hemorrhage (all P>0.05). Conclusion: For ACS patients after PCI, clopidogrel resistance can increase the risk of combined thrombotic events, but also reduce the risk of bleeding; while CYP2C19 genotype is not an independent factor for clinical prognosis.
Acute Coronary Syndrome/genetics* ; Clopidogrel/therapeutic use* ; Cytochrome P-450 CYP2C19/genetics* ; Genotype ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prognosis ; Retrospective Studies ; Treatment Outcome

Depression is prevalent in patients with physical disorders, particularly in those with severe disorders such as cancer, stroke, and acute coronary syndrome. Depression has an adverse impact on the courses of these diseases that includes poor quality of life, more functional impairments, and a higher mortality rate. Patients with physical disorders are at higher risk of depression. This is particularly true for patients with genetic and epigenetic predictors, environmental vulnerabilities such as past depression, higher disability, and stressful life events. Such patients should be monitored closely. To appropriately manage depression in these patients, comprehensive and integrative care that includes antidepressant treatment (with considerations for adverse effects and drug interactions), treatment of the physical disorder, and collaborative care that consists of disease education, cognitive reframing, and modification of coping style should be provided. The objective of the present review was to present and summarize the prevalence, risk factors, clinical correlates, current pathophysiological aspects including genetics, and treatments for depression comorbid with physical disorders. In particular, we tried to focus on severe physical disorders with high mortality rates, such as cancer, stroke, and acute coronary syndrome, which are highly comorbid with depression. This review will enhance our current understanding of the association between depression and serious medical conditions, which will allow clinicians to develop more advanced and personalized treatment options for these patients in routine clinical practice.
Acute Coronary Syndrome ; Comorbidity ; Depression ; Education ; Epigenomics ; Genetics ; Humans ; Mortality ; Prevalence ; Prognosis ; Quality of Life ; Risk Factors ; Stroke

OBJECTIVETo investigate serum level and gene polymorphisms of matrix metalloproteinase 9 (MMP-9), and platelet glycoprotein VI (GPVI) in patients with acute coronary syndrome (ACS).

METHODSIn a prospective study of 179 patients with documented ACS and 164 controls, we measured baseline serum MMP-9 levels using ELISA and determined the MMP-9/C-1562T and MMP-9/G5564A genotypes using PCR-restriction fragment length polymorphism. Fib serum level was measured by Clauss assay. We also analyzed the Fib/Bbeta-148C/T and GPVI/T13254C polymorphisms.

RESULTSSerum levels of MMP-9 and Fib in ACS patients were significantly higher than in controls (P < 0.001), and serum level of Fib in the acute myocardial infarction group was higher than in patients with unstable angina (P < 0.05). No significant difference between ACS patients and controls was found in frequencies of MMP-9/C-1562T, MMP-9/G5564A, Fib/Bbeta-148C/T, and GPVI/T13254C genotypes and alleles (P > 0.05). The T allele of the Fib/Bbeta-148T polymorphism was associated with increased plasma Fib level (P < 0.05). There was a strong positive correlation between serum level of MMP-9 and Fib (r = 0.289, P < 0.01).

CONCLUSIONSerum levels of MMP-9 and Fib were independent risk factors of ACS. There was an obvious relationship between the Bbeta-148C/T mutation and high Fib level. No significant difference between controls and ACS patients was found in the frequencies of MMP-9 C-1562T and G5564A, Fib Bbeta-148C/T and GPVI T13254C genotypes and alleles (P > 0.05).

Acute Coronary Syndrome ; genetics ; Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; genetics ; Middle Aged ; Platelet Membrane Glycoproteins ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the association between CD147 expression and its untranslated regions 3'UTR rs8259 T/A polymorphism and acute coronary syndrome (ACS).

METHODSThe genotypes of CD147 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 182 ACS patients and 328 healthy controls. The plasma level of CD147 was determined by enzyme-linked immunosorbent assay (ELISA). CD147 mRNA and protein expression was detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot.

RESULTSThe plasma CD147 level obtained from radial artery in ACS patients ((3.63 ± 0.70) pg/L) was significantly higher than in control ((2.45 ± 0.27) pg/L, P < 0.05), and highest in plasma obtained from the coronary artery ((4.28 ± 1.03) pg/L, P < 0.05) in ACS patients. Furthermore, the plasma CD147 level was higher in the ACS patients with rs8259 AA genotype than in the ACS patients with rs8259 TT genotype ((4.08 ± 0.41) pg/L vs. (3.05 ± 0.79) pg/L in radial artery and (5.29 ± 0.62) pg/L vs. (3.13 ± 0.52) pg/L in coronary artery, both P < 0.05). There are an enhanced expression of CD147 mRNA (2.45 times higher than control) and protein (3.66 ± 1.56 vs. 1.81 ± 1.29) in PBMCs from ACS patients than that from controls (both P < 0.05). The PBMCs CD147 mRNA and protein expression level were significantly higher in ACS patients with rs8259 AA genotype (mRNA:2.45 ± 0.35, protein:1.63 ± 0.16) compared to ACS patients with rs8259 TT genotype (mRNA:1.69 ± 0.15, protein: 0.88 ± 0.16, both P < 0.05). Multiple logistic analysis showed that CD147 T allele (AT+TT) was a protective factor to ACS (OR = 0.667, 95% CI 0.507-0.879, P < 0.05).

CONCLUSIONSThe over-expression of CD147 is involved in the pathogenesis of ACS. The CD147 3'UTR rs8259 T allele may be a protective factor for ACS, its polymorphism can affect the CD147 protein expression in ACS patients.

Acute Coronary Syndrome ; genetics ; Alleles ; Basigin ; biosynthesis ; genetics ; Case-Control Studies ; Genotype ; Humans ; Leukocytes, Mononuclear ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo assess the value of serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and LOX-1 mRNA expression in peripheral blood mononuclear cells in early diagnosis of acute coronary syndrome (ACS).

METHODSEnzyme-linked immunosorbent assay was used to detect the levels of plasma ox-LDL and LOX-1 in 95 patients with ACS, 60 with stable angina pectoris (SAP) and 40 normal control subjects. The expression of LOX-1 mRNA in peripheral blood mononuclear cells was detected by RT-PCR in the 3 groups.

RESULTSThe levels of ox-LDL, LOX-1 and LOX-1 mRNA in the peripheral blood mononuclear cells were significantly higher in ACS patients than in SAP patients and normal control subjects (P<0.05). In ACS group, the level of plasma ox-LDL was significantly correlated to serum LOX-1 and LOX-1 mRNA expression in peripheral mononuclear cells.

CONCLUSIONThe level of plasma soluble LOX-1 and LOX-1 mRNA in peripheral mononuclear cells are significantly increased in ACS, and when combined, they provide a useful means for detecting ACS in the prophase.

Acute Coronary Syndrome ; blood ; diagnosis ; Aged ; Early Diagnosis ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Scavenger Receptors, Class E ; blood

BACKGROUNDThe CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients.

METHODSIn 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.

RESULTSGenotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%).

CONCLUSIONCoexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Acute Coronary Syndrome ; drug therapy ; genetics ; Aged ; Alleles ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C19 ; Genotype ; Humans ; Middle Aged ; Mutation ; Polymorphism, Genetic ; genetics ; Receptors, Purinergic P2Y12 ; genetics ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo investigate the relationship between plasma cytochrome P450 3A4 (CYP3A4) 894C>T gene polymorphism and the risk of recurrence of adverse cardiac events after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS).

METHODSA total of 275 patients with ACS received standard dual antiplatelet therapy and PCI. Platelet aggregation rate (PAR) was detected in each patient before and 7 days after administration of the anti-platelet drugs. Single nucleotide polymorphism of CYP3A4 gene 894C>T was detected with PCR and microarray technique. The number of coronary artery lesions was determined by PCI and the Gensini score was calculated. The patients were followed up for 3-12 months after discharge.

RESULTSNo significant difference was found in CYP3A4 gene polymorphism between patients with clopidogrel resistance (CR group) and those without CR (NCR group) (P>0.05). Multivariate logistic regression analysis showed that CYP3A4 gene 894C>T polymorphism was not correlated with CR in patients with ACS (OR 1.359, P>0.05). During the follow-up, the incidence of cardiovascular events was significantly higher in CR group than in NCR group (P<0.05), but this difference was not related to the mutation type of 894C>T locus of CYP3A4 gene.

CONCLUSIONThe CYP3A4 gene 894C>T polymorphism is not associated with the effect of anti-platelet therapy and the risk of cardiovascular event in patients with ACS following PCI.

Acute Coronary Syndrome ; therapy ; Alleles ; Blood Platelets ; Cytochrome P-450 CYP3A ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Function Tests ; Polymorphism, Single Nucleotide ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the expressions of sterol regulatory element binding protein-2 (SREBP-2) and hydroxymethylglutaryl CoA reductase (HMGCR) in the macrophages derived from monocytes of patients with acute coronary syndrome (ACS).

METHODSLDL was oxidized by Cu2+ to prepare ox-LDL, and peripheral monocytes were isolated by density gradient centrifugation from patients with ACS diagnosed by coronary arteriography. Macrophages derived from the monocytes after phorbol myristate acetate (PMA) stimulation were treated with ox-LDL at the concentrations of 0, 20, 40, and 100 ng/ml, and the changes in the expressions of SREBP-2 and HMGCR were detected by real-time RT-PCR.

RESULTSCompared with the control cells, the macrophages treated with ox-LDL showed significantly increased expressions of SREBP-2 and HMGCR mRNA (P<0.05). In cells treated with ox-LDL, the expressions of SREBP-2 and HMGCR mRNA differed significantly with the dose administered (P<0.05).

CONCLUSIONWithin a defined dose range, ox-LDL can dose-dependently enhance the expressions of SREBP-2 and HMGCR mRNA in macrophages from patients with ACS.

Acute Coronary Syndrome ; blood ; Dose-Response Relationship, Drug ; Humans ; Hydroxymethylglutaryl CoA Reductases ; genetics ; metabolism ; Lipoproteins, LDL ; pharmacology ; Macrophages ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; genetics ; metabolism