The role and mechanisms of microvascular damage in the ischemic myocardium.

Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5-50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.

A prediction model to predict in-hospital mortality in patients with acute type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (ABAD) is a life-threatening cardiovascular disease. A practicable and effective prediction model to predict and evaluate the risk of in-hospital death for ABAD is required. The present study aimed to construct a prediction model to predict the risk of in-hospital death in ABAD patients. METHODS: A total of 715 patients with ABAD were recruited in the first affiliated hospital of Xinjiang medical university from April 2012 to May 2021. The information on the demographic and clinical characteristics of all subjects was collected. The logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and nomogram were applied to screen the appropriate predictors and to establish a prediction model for the risk of in-hospital mortality in ABAD. The receiver operator characteristic curve and calibration plot were applied to validate the performance of the prediction model. RESULTS: Of 53 (7.41%) subjects occurred in-hospital death in 715 ABAD patients. The variables including diastolic blood pressure (DBP), platelets, heart rate, neutrophil-lymphocyte ratio, D-dimer, C-reactive protein (CRP), white blood cell (WBC), hemoglobin, lactate dehydrogenase (LDH), procalcitonin, and left ventricular ejection fraction (LVEF) were shown a significant difference between the in-hospital death group and the in-hospital survival group (all P < 0.05). Furthermore, all these factors which existed differences, except CRP, were associated with in-hospital deaths in ABAD patients (all P < 0.05). Then, parameters containing LVEF, WBC, hemoglobin, LDH, and procalcitonin were identified as independent risk factors for in-hospital deaths in ABAD patients by adjusting compound variables (all P < 0.05). In addition, these independent factors were qualified as predictors to build a prediction model (AUC > 0.5, P < 0.05). The prediction model was shown a favorable discriminative ability (C index = 0.745) and demonstrated good consistency. CONCLUSIONS: The novel prediction model combined with WBC, hemoglobin, LDH, procalcitonin, and LVEF, was a practicable and valuable tool to predict in-hospital deaths in ABAD patients.

A prediction model based on platelet parameters, lipid levels, and angiographic characteristics to predict in-stent restenosis in coronary artery disease patients implanted with drug-eluting stents.

BACKGROUND: The present study was aimed to establish a prediction model for in-stent restenosis (ISR) in subjects who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). MATERIALS AND METHODS: A retrospective cohort study was conducted. From September 2010 to September 2013, we included 968 subjects who had received coronary follow-up angiography after primary PCI. The logistic regression analysis, receiver operator characteristic (ROC) analysis, nomogram analysis, Hosmer-Lemeshow χ2 statistic, and calibration curve were applied to build and evaluate the prediction model. RESULTS: Fifty-six patients (5.79%) occurred ISR. The platelet distribution width (PDW), total cholesterol (TC), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and lesion vessels had significant differences between ISR and non-ISR groups (all P < 0.05). And these variables were independently associated with ISR (all P < 0.05). Furthermore, they were identified as predictors (all AUC > 0.5 and P < 0.05) to establish a prediction model. The prediction model showed a good value of area under curve (AUC) (95%CI): 0.72 (0.64-0.80), and its optimized cut-off was 6.39 with 71% sensitivity and 65% specificity to predict ISR. CONCLUSION: The incidence of ISR is 5.79% in CAD patients with DES implantation in the Xinjiang population, China. The prediction model based on PDW, SBP, TC, LDL-C, and lesion vessels was an effective model to predict ISR in CAD patients with DESs implantation.

Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation.

BACKGROUND: Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H2O2) by inhibiting the NF-κB pathway. METHODS: The IκBαS32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H2O2 treatment. NRVMs were divided into control, H2O2, GFP + H2O2, IκBα+H2O2, and pyrrolidine dithiocarbamate (PDTC) + H2O2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins. RESULTS: IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H2O2. Meanwhile, IκBα overexpression decreased H2O2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H2O2 stimulation. CONCLUSION: IκBα overexpression can ameliorate H2O2-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.

Cardioprotective effects of constitutively active MEK1 against H2O2-induced apoptosis and autophagy in cardiomyocytes via the ERK1/2 signaling pathway.

Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (H2O2) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms. As a result, CaMEK attenuated H2O2-induced apoptosis and cytotoxicity in NCMs, evidenced by decreased apoptotic cells and the ratio of Bax/Bcl-2, increased the mitochondrial membrane potential (Δψm) and cell vitality and reduced the level of lactate dehydrogenase (LDH). Further studies revealed that CaMEK attenuated H2O2-induced autophagy, evidenced by the decreased LC3-Ⅱ/LC3-Ⅰratio and SQSTM1/p62 (p62) degradation. Furthermore, we demonstrated that CaMEK phosphorylated the ERK1/2 pathway-related proteins, ERK1/2, p70S6K and GSK3ß, in NCMs with H2O2 stimulation. In contrast, these effects could be reversed by co-treatment with the ERK1/2 inhibitor, PD98059. These results suggest that CaMEK plays an important role in protecting cardiomyocytes against H2O2-induced injury and autophagy in NCMs via ERK1/2 pathway. Therefore, transfection of CaMEK may provide a hopeful therapeutic strategy for I/R.

Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning-mediated cardioprotection.

Ischemic preconditioning (IPC) is an endogenous protection strategy against myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) released from the myocardium subjected to brief periods of ischemia confers cardioprotection. We hypothesized that MIF plays an essential role in IPC-induced cardioprotection. I/R was induced either ex vivo or in vivo in male wild-type (WT) and MIF knockout (MIFKO) mice with or without proceeding IPC (three cycles of 5-min ischemia and 5-min reperfusion). Indices of myocardial injury, regional inflammation and cardiac function were determined to evaluate the extent of I/R injury. Activations of the reperfusion injury salvage kinase (RISK) pathway, AMP-activated protein kinase (AMPK) and their downstream components were investigated to explore the underlying mechanisms. IPC conferred prominent protection in WT hearts evidenced by reduced infarct size (by 33-35%), myocyte apoptosis and enzymatic markers of tissue injury, ROS production, inflammatory cell infiltration and MCP1/CCR2 expression (all P<0.05). IPC also ameliorated cardiac dysfunction both ex vivo and in vivo These protective effects were abolished in MIFKO hearts. Notably, IPC mediated further activations of RISK pathway, AMPK and the membrane translocation of GLUT4 in WT hearts. Deletion of MIF blunted these changes in response to IPC, which is the likely basis for the absence of protective effects of IPC against I/R injury. In conclusion, MIF plays a critical role in IPC-mediated cardioprotection under ischemic stress by activating RISK signaling pathway and AMPK. These results provide an insight for developing a novel therapeutic strategy that target MIF to protect ischemic hearts.

Apolipoprotein A1 is associated with SYNTAX score in patients with a non-ST segment elevation myocardial infarction.

BACKGROUND: The study was designed to investigate lipid profile and SYNTAX score in patients with non-ST segment elevation myocardial infarction (NSTEMI). METHODS: 311 patients with NSTEMI were enrolled. The demographic, clinical data, blood samples and SYNTAX score were documented. The Pearson linear correlation was used to detect confounding factors linearly correlated with SYNTAX score. The significantly correlated confounding factors were put into the multiple linear regressions. RESULTS: The Pearson linear correlation showed that high-density lipoprotein- cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) were significantly correlated with Syntax Score (r = - 0.119, P = 0.044 and r = - 0.182, P = 0.002, respectively). The multiple linear regressions for Syntax Score were built using HDL-C and ApoA1, respectively. After the adjustment of other significantly correlated confounding factors such as white blood cell count (WBC), myohemoglobin (MB), glutamic-oxalacetic transaminase (AST) and creatinine, the ApoA1 still showed significant association with Syntax Score (ß = - 0.151, P = 0.028). The area under curve was (AUC) 0.624 and the optimal cutoff value is 1.07 g/L when using ApoA1 to predict moderate and severe coronary artery lesions. The patients with ApoA1 ≥ 1.07 g/L and < 1.07 g/L have the Syntax Scores of 12.21 ± 11.58 and 16.33 ± 11.53, respectively (P = 0.001). CONCLUSIONS: The ApoA1 is the only lipid factor significantly associated with complexity of coronary artery lesion in patients with NSTEMI, the patients with ApoA1 < 1.07 g/L may have more complex coronary artery lesions.

Targeting transgene to the heart and liver with AAV9 by different promoters.

Adeno-associated virus (AAV) has become one of the most promising gene transfer tools for gene therapy. This work aims to evaluate tropism, gene transfer efficiency and safety of AAV9 vectors produced with recombinant baculovirus (rBac)-based system. AAV9-CMV-GFP and AAV9-CBA-GFP were produced using a rBac system, 1 × 10(11) particles of each vectors were administered intravenously (i.v.) into mice and animals were killed at 1, 2, 3, 4, 5 and 8 weeks after administration. The GFP expression in different organs was analyzed by fluorescence imaging and Western blot. Viral genomic quantities were measured using qPCR. In vitro transduction efficiency of AAV9 vectors in primary cardiomyocytes and hepatocytes was determined by flow cytometry. Toxicity of AAV9 vectors was evaluated by determining certain cardiac and liver injury biomarkers and renal function test in vivo and TUNEL analysis in vitro. The data showed that AAV9 viral particles packaged by the rBac system were fully functional in vivo and in vitro. The CMV promoter predominantly induced higher cardiac GFP transgene expression and DNA copy numbers while the CBA promoter resulted in robust GFP expression and high vector DNA copy numbers in mouse liver, both in a time-dependent increased manner. Such distinct preferential effects were also observed in the heart and liver as early as 3 and 5 days after co-infection. Both the AAV9-CMV and AAV9-CBA viral packages did not induce heart, liver and renal damage and cell apoptosis. These results indicated that AAV9-CMV can efficiently and safely direct cardiac gene transfer, whereas AAV9-CBA is preferential for liver gene delivery.

Relationship between CYP17A1 genetic polymorphism and coronary artery disease in a Chinese Han population.

BACKGROUND: CYP17A1 gene encodes P450c17 proteins, which is a key enzyme that catalyzes the formation of sex hormones. Many clinical studies showed that sex hormones levels play an important role in the pathogenesis of coronary artery disease (CAD). However, the relationship between CYP17A1 genetic polymorphisms and CAD remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with CAD in a Han population of China. METHODS: A total of 997 people include 490 patients and 507 controls were selected for the present study. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped by using the real-time PCR (TaqMan) method. RESULTS: For men, the rs10786712 was found to be associated with CAD in a recessive model (P=0.016), after adjustment of the major confounding factors, the significant difference was retained (OR=1.644, 95% confidence interval [CI]: 1.087-2.488, P=0.019). For women, the rs1004467 was also found to be associated with CAD in a dominant model (P=0.038), the difference remained statistically significant after multivariate adjustment (OR=1.623, 95% CI: 1.023-2.576, P=0.040). The distribution of rs4919687 genotypes showed a significant difference between CAD and control participants in a recessive model (P=0.019), the significant difference was retained after adjustment for covariates (OR=0.417, 95% CI: 0.188-0.926, P=0.032). CONCLUSION: Rs1004467, rs4919687, rs10786712 of CYP17A1 gene are associated with CAD in Han population of China. The TT genotype of rs10786712 could be a protective genetic marker of CAD in men. The CC genotype of rs1004467 and the AA genotype of rs4919687 could be risk genetic markers of CAD in women. However, large sample size study including other SNPs of CYP17A1 should be performed in future studies.

The diagnostic and prognostic value of SAA1 as a novel biomarker for acute aortic dissection.

BACKGROUND AND AIMS: Acute aortic dissection (AAD) is a serious life-threatening cardiovascular condition. It is necessary to find rapid and accurate biomarkers for the diagnosis of AAD. This study aimed to determine the efficacy of serum amyloid A1 (SAA1) in the diagnosis and prediction of long-term adverse events in AAD. MATERIALS AND METHODS: Four-dimensional label-free quantification (4D-LFQ) technique was used to identify the differentially expressed proteins (DEPs) in aortic tissues of AAD. After comprehensive analysis, SAA1 was identified as a potential biomarker of AAD. ELISA was used to confirm the expression of SAA1 in serum of AAD patients. Moreover, the source of SAA1 in serum was explored by constructing AAD mouse model. RESULTS: A total of 247 DEPs were identified, of which 139 were upregulated while 108 were downregulated. SAA1 was nearly 6.4-fold and 4.5-fold upregulated in AAD tissue and serum. ROC curve and Kaplan-Meier survival curve confirmed the good efficacy of SAA1 for the diagnosis and prediction of long-term adverse events in AAD. In vivo experiments revealed that SAA1 was mainly derived from the liver when AAD occurred. CONCLUSION: SAA1 can be used as a potential biomarker for AAD with effective diagnostic and prognostic value. SIGNIFICANCE: Despite the advances in medical technology in recent years, the mortality rate of acute aortic dissection (AAD) is still high. It is still challenging for clinicians to diagnose AAD patients on time and reduce the mortality rate. In this study, 4D-LFQ technology was used to identify serum amyloid A1 (SAA1) as a potential biomarker of AAD and was verified in subsequent work. The results of this study determined the efficacy of SAA1 in the diagnosis and prediction of long-term adverse events in patients with AAD.

Polymorphisms of rs2483205 and rs562556 in the PCSK9 gene are associated with coronary artery disease and cardiovascular risk factors.

PCSK9 plays a crucial role in lipid metabolism. This case-control study explored the associations of novel single nucleotide polymorphisms (SNPs) of the PCSK9 gene with coronary artery disease (CAD) (≥ 1 coronary artery stenosis ≥ 50%) and its risk factors in the Han population in Xinjiang, China. Four tag SNPs (rs11583680, rs2483205, rs2495477 and rs562556) of the PCSK9 gene were genotyped in 950 CAD patients and 1082 healthy controls. The distributions of genotypes in rs2483205 and rs562556 were significantly different between the groups (all p < 0.05). The TT genotype of rs2483205, GG genotype of rs562556, and their H4 (T-G) haplotype were associated with CAD [odds ratio (OR) 0.65, confidence interval (CI) 0.45-0.95, p = 0.024; 0.63, 0.45-0.90, p = 0.011; 0.50, 0.35-0.70, p < 0.001, respectively]. Additionally, the model (TT + CT vs. CC) of rs2483205 was associated with increased risk of obesity, and the G allele of rs562556 was associated with lower low-density lipoprotein cholesterol (LDL-C), blood glucose, body mass index (BMI), and mean platelet volume (MPV) (all p < 0.05). rs2483205, rs562556, and their H4 haplotype of the PCSK9 gene were associated with CAD. Additionally, rs2483205 is associated with obesity, and rs562556 is associated with LDL-C, blood glucose, BMI, and MPV.

Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China.

Dyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.

APLP2 gene polymorphisms are associated with high TC and LDL-C levels in Chinese population in Xinjiang, China.

Hyperlipidemia is one of the main risk factors for coronary artery disease (CAD). In the present study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) in amyloid precursor-like protein (APLP) 2 (APLP2) gene were associated with high lipid levels in Chinese population in Xinjiang, China. We recruited 1738 subjects (1187 men, 551 women) from the First Affiliated Hospital of Xinjiang Medical University, and genotyped three SNPs (rs2054247, rs3740881 and rs747180) of APLP2 gene in all subjects by using the improved multiplex ligation detection reaction (iMLDR) method. Our study revealed that the rs2054247 SNP was associated with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels, and high-density lipoprotein cholesterol (HDL-C) in additive model (all P<0.05). The rs747180 SNP was associated with serum TC and LDL-C levels in additive model (all P<0.05). Our study revealed that both rs2054247 and rs747180 SNPs of the APLP2 gene were associated with high TC and LDL-C levels in Chinese subjects in Xinjiang.

TT genotype of rs2941484 in the human HNF4G gene is associated with hyperuricemia in Chinese Han men.

The aim of the study is to investigate the association between the human hepatocyte nuclear factor 4 gamma (HNF4G) gene and hyperuricemia in Chinese Han population. A total of 414 hyperuricemia patients and 406 gender and age-matched normouricemic controls were enrolled. Four single nucleotide polymorphisms were genotyped as genetic markers for the human HNF4G gene (rs2977939, rs1805098, rs2941484, rs4735692). Data were analyzed for two separate groups: men and women. For rs2941484, the genotype distribution frequency in hyperuricemic subjects and was significantly different from that in normouricemic controls in men (P = 0.038). Meanwhile, in recessive model of rs2941484, the distribution frequency of TT genotype and CC+CT genotypes also differed significantly between the hyperuricemia men and normouricemic men (P = 0.011). For the other 3 SNPs in both men and women, there was no difference in the genotype and allele and distribution frequency between the hyperuricemia patients and normouricemic controls. In men, after adjustments for BMI, SBP, DBP, fasting glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol and creatinine, the men with the TT genotype of rs2941484 were found to have significantly higher probability of suffering from hyperuricemia than the ones with CT and CC genotypes (OR = 2.170, P < 0.001). Therefore, TT genotype of rs2941484 in the human HNF4G gene might be a gender-specific genetic marker for hyperuricemia in Chinese Han men.

4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats.

BACKGROUND: Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. CONCLUSION: Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries.

Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis.

Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility.

Relationship between CYP17A1 Genetic Polymorphism and Essential Hypertension in a Chinese Population.

The relationship between CYP17A1 genetic polymorphisms and essential hypertension (EH) remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with EH in Han and Uighur populations in China. A Han population including 558 people (270 EH patients and 288 controls) and a Uighur population including 473 people (181 EH patients and 292 controls) were selected. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped using real-time PCR (TaqMan). In the Uighur population, for the total and the men, rs4919686, rs4919687 and rs10786712 were found to be associated with EH (rs4919686: P≤0.02, rs4919687: P≤0.002, rs10786712: P≤0.004, respectively). The difference remained statistically significant after the multivariate adjustment (all P<0.05). The overall distributions of the haplotypes established by SNP1-SNP3, SNP1-SNP4, SNP1-SNP3-SNP5 and SNP1-SNP4-SNP5 were significantly different between the EH patients and the control subjects (for the total: P=0.013, P=0.008, P=0.032, P=0.010, for men: P<0.001, P=0.001, P=0.010, P=0.00). In the Han population, for men, rs2486758 was found to be associated with EH in a recessive model (P=0.007); the significant difference was not retained after the adjustment for the covariates (date not shown). The A allele of rs4919686 could be a susceptible genetic marker, and the T allele of rs10786712 could be a protective genetic marker of EH. The AC genotype of rs4919686, the AG genotype of rs4919687 and the TT genotype of rs10786712 could be protective genetic markers of EH.

Association between ErbB3 genetic polymorphisms and coronary artery disease in the Han and Uyghur populations of China.

BACKGROUND: ErbB3 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. Recent research has shown that amplification of this gene is related to prostate, bladder and breast cancers, as well as low-density lipoprotein cholesterol (LDL-C) metabolism. LDL-C plays a considerable role in the development of cardiovascular disease. Thus, the present study assessed the association between human ErbB3 gene polymorphisms and coronary artery disease (CAD) in Han and Uygur populationsin China. METHODS: We performed two independent case-control studies with a Han population (339 CAD patients and 395 control subjects) and a Uygur population (306 CAD patients and 325 control subjects). All of the CAD patients and controls were genotyped for the same three single nucleotide polymorphisms (rs877636, rs705708, and rs10783779) in the ErbB3 gene by real-time PCR. RESULTS: In the Han population, rs877636 polymorphisms were associated with CAD on the basis of the genotypes, dominant model, additive model, and allele frequency (for genotypes: P = 0.008; for dominant model: P = 0.003; for additive model: P = 0.004; for allele: P = 0.008), and these significant difference was retained (all P < 0.05) after adjusting for the major confounding factors. CONCLUSION: The CT genotype and C allele of rs877636 in the ErbB3 gene could be a genetic marker of CAD risk for the Han population in China.

The relationship between the polymorphisms of the CYP17A1 gene and hypertension: A meta-analysis.

OBJECTIVE: With the development of genome-wide association studies (GWAS) concerning hypertension, a growing number of susceptibility genes related to hypertension have been revealed. Subsequently, several studies have investigated the association between CYP17A1 rs1004467 heritable variation and hypertension; however, the results have been inconsistent. In this study, a meta-analysis was performed to assess the association between the CYP17A1 rs1004467 polymorphism and hypertension risk. METHODS: The PubMed, ISI Web of Science and Embase databases as well as China Wanfang, Weipu and the Chinese Journal Full-text Database were used to retrieve all publications from 2005 to 2013 related to case-control studies that reported a link between the risk factors for hypertension and the CYP17A1 polymorphism. All association studies were identified, and a meta-analysis was conducted using the RevMan 5.0 estimate for odds ratios (ORs) to determine whether the A allele predicts hypertension outcomes. RESULTS: Three articles including five studies (totaling 4495 patients and 3529 controls) were identified. The overall effect suggested that rs1004467 was significantly associated with hypertension (OR=1.22, 95%CI 1.08-1.38, p=0.001). CONCLUSIONS: The present meta-analysis confirmed the significant association between a polymorphism of the CYP17A1 gene and hypertension susceptibility. The CYP17A1 A allele should be considered a risk factor for hypertension.

Haplotype analyses of CYP17A1 genetic polymorphisms and coronary artery disease in a Uygur population.

BACKGROUND: The relationship between CYP17A1 genetic polymorphisms and coronary artery disease (CAD) remains unclear. The aim of the present study was to assess the association between CYP17A1 gene polymorphism and CAD in a Chinese Uygur population. METHODS: A total of 493 people including 266 patients and 227 controls were selected for the present study. All CAD patients and controls were genotyped for the same five single nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) by a real-time PCR method. RESULTS: The rs4919686, rs1004467, and rs4919687 polymorphisms were found to be associated with CAD in genotypes, dominant model, recessive model, and allele frequency (rs4919686: all p<0.05, rs1004467: all p ≤ 0.001, rs4919687: all p<0.001); the significant difference was retained (all p<0.05) after adjustment for the major confounding factors. The overall distribution of haplotypes established by SNP1-SNP4 (in total subjects and men) and SNP1-SNP4-SNP5 (in total subjects) were significantly different between the CAD patients and the control subjects (p=0.006, men: p=0.026, and p=0.030, respectively). CONCLUSION: Polymorphisms rs4919686, rs4919687 and rs1004467 were found to be associated with CAD in this Uygur population.