Qingjie Chen

−94 ATTG Insertion/Deletion Polymorphism of the NFKB1 Gene Is Associated with Coronary Artery Disease in Han and Uygur Women in China

OBJECTIVES The nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) signaling pathway plays a key role in the regulatory network of inflammation. The deletion variant allele of the NFKB1-94 insertion/deletion (ins/del) ATTG promoter polymorphism results in lower transcription levels of the p50 subunit, and the variant allele has been associated with several inflammatory diseases as well as with coronary artery disease (CAD) with inflammation playing an important part in the pathogenesis. The aim of the present study was to assess the association between the human NFKB1 gene polymorphism and CAD in a Han and Uygur population of China. METHODS We used the following two independent case-control studies: a Han population (633 CAD patients and 616 control subjects) and a Uygur population (437 CAD patients and 356 control subjects). All participants were genotyped for the same one single nucleotide polymorphism (SNP) (rs28362491) of the NFKB1 gene, that is, DD, ATTG deleted homozygote; ID, ATTG inserted and deleted heterozygote and II, ATTG inserted homozygote by real-time polymerase chain reaction. RESULTS The distribution of the SNP (rs28362491) genotypes was significantly different between CAD and control participants in women of the Han (p=0.029) and the Uygur (p=0.032) populations, but not in men. Further, DD carriers of the SNP in the NFKB1 gene were more frequent in female CAD patients than in controls in both the Han (23.2% vs. 13.5%, p=0.009) and the Uygur (19.8% vs. 8.3%, p=0.012) population. The significant difference between DD and ID+II genotypes was retained after adjustment for covariates (for Han, odds ratio [OR]: 1.805, p=0.029 and for Uygur, OR: 3.192, p=0.011). CONCLUSIONS The DD genotype of the SNP (rs28362491) in the NFKB1 gene may be considered a genetic marker of CAD in Han and Uygur women in China.

Association of mean platelet volume with angiographic thrombus burden and short-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

The aim of this study was to evaluate the impact of mean platelet volume (MPV) on the intracoronary thrombus burden and short‐term mortality in patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Prognostic nutritional index predicts clinical outcome in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

We aimed to investigate whether the prognostic nutritional index (PNI), a combined nutritional-inflammatory score based on serum albumin levels and lymphocyte count, was associated with mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). From September 2011 to November 2014, 309 consecutive patients with STEMI undergoing pPCI were prospectively enrolled. Patients with a combined score of albumin (g/L) + 5 × total lymphocyte count × 109/L ≥ 45 or <45 were assigned a PNI score of 0 or 1, respectively. Of the 309 STEMI patients, 24 (7.74%) died in the hospital, and 15 (4.83%) died during long-term follow-up (median follow-up time, 19.5 [3–36] months). Compared to patients with a PNI of 0, patients with a PNI of 1 had significantly higher in-hospital (14.2% vs. 3.7%; P < 0.001) and long-term follow-up (21.7% vs. 6.9%, P < 0.001) mortality rates. PNI (1/0, HR, 2.414; 95% CI, 1.016 to 5.736; P = 0.046) was a significant independent predictor of mortality in patients with STEMI undergoing pPCI. Moreover, cumulative survival was significantly lower for patients with a PNI of 1 compared to patients with a PNI of 0 (78.3% vs. 93.1%, log-rank P < 0.001). PNI appears useful for the risk stratification of STEMI patients undergoing pPCI.

Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China

Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD). Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD) risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged ≥35 years were selected from the Cardiovascular Risk Survey (CRS) study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL-C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL-C ratio. Our study also demonstrated that the discriminatory power of the LDL-C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or ≥two of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang.

Association of mean platelet volume with impaired myocardial reperfusion and short-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Impaired myocardial reperfusion, defined angiographically by myocardial blush grade (MBG) 0 or 1, is associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the impact of admission mean platelet volume (MPV) on the myocardial reperfusion and 30-day all-cause mortality in patients with STEMI with successful epicardial reperfusion after primary percutaneous coronary intervention (PCI). A total of 453 patients with STEMI who underwent primary PCI within 12 h of symptoms onset and achieved thrombolysis in myocardial infarction (TIMI) 3 flow at infarct-related artery after PCI were enrolled and divided into two groups based on postinterventional MBG: those with MBG 2/3 and those with MBG 0/1. Admission MPV was measured before coronary angiography. The primary endpoint was all-cause mortality at 30 days. MPV was significantly higher in patients with MBG 0/1 than in patients with MBG 2/3 (10.38 ± 0.98 vs. 9.59 ± 0.73, P < 0.001). The cumulative 30-day all-cause mortality rate was significantly higher in the groups with high MPV and MBG 0/1 (6.8 vs. 1.5%, P = 0.005, 7.6 vs. 1.9%, P = 0.006, respectively). Multivariate logistic regression analysis demonstrated MPV was independently associated with postinterventional impaired myocardial reperfusion (odds ratio 2.684, 95% confidence interval 2.010–3.585, P < 0.001) and 30-day all-cause mortality (hazard ratio 1.763, 95% confidence interval 1.009–3.079, P = 0.046). Increased MPV on admission is an independent predictor of impaired myocardial reperfusion and short-term mortality in patients with STEMI with successful epicardial reperfusion after primary PCI. Admission MPV may be additive to conventional risk factors in patients with STEMI undergoing PCI.

Expression pattern of genome-scale long noncoding RNA following acute myocardial infarction in Chinese Uyghur patients

In this study, we examined the long noncoding RNA (lncRNA) expression pattern in Uyghur patients (a minority of China) with acute myocardial infarction (AMI) on a genome-wide scale. Total RNAs were extracted from the peripheral blood of 55 Uyghur AMI patients and 55 healthy volunteers. The expression levels of genome-wide scale lncRNAs and mRNAs were determined by microarray in 10 samples (5 AMI and 5 controls). qRT-PCR was used to validate lncRNA expression levels in 100 samples (50 AMI and 50 controls). Data analyses were performed using R and Bioconductor. A total of 3624 up- and 1637 down-regulated lncRNAs were identified to be significantly and differentially expressed between these two groups. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was regulation of biological processes, and the most significantly related pathway was apoptosis and its corresponding p53. The microarray identified ENST00000416860.2, ENST00000421157.1 and TCONS_00025701 lncRNAs were confirmed by qRT-PCR. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in the peripheral blood of AMI patients when compared with healthy controls within the Uyghur population. These newly identified lncRNAs may have a potential role in the development of AMI.

Association Between the NFKB1-94ins/del ATTG Polymorphism (rs28362491) and Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND Inflammation plays an important role in the pathophysiology of coronary artery disease (CAD). NF-κB is a central regulator of inflammation. Thus the aim of this study was to conduct a systematic review and meta-analysis investigating whether the polymorphism in the NFKB1 promoter region (NFKB1-94ins(I)/del(D)ATTG, rs28362491) is associated with CAD susceptibility. METHODS PubMed, Embase, Cochrane Library and CNKI databases were searched up to 30 July 2015. All observational case-control studies that investigated the association of NFKB1 I/D polymorphism and CAD risk were included. Two reviewers independently selected the studies and extracted the data. RESULTS A total of 7 studies were included in this meta-analysis. Comparison between alleles showed a 13% increased risk of CAD for D vs. I (OR = 1.13, 95% CI 1.06-1.19, PH = 0.318), and comparisons among genotypes showed a 26% increased risk of CAD for DD vs. II (OR = 1.26, 95% CI 1.12-1.43, PH = 0.125) and in the heterozygote model ID vs. II had an 11% increased risk (OR = 1.11, 95% CI 1.01-1.21, PH = 0.751). In the dominant model the risk of CAD risk was reduced by 13% (OR = 0.87, 95%CI 0.80-0.95, PH = 0.814) across the total population. Subgroup analysis by ethnicity indicated that the additive model was associated with a 21% increased risk for CAD in the Caucasian population (OR = 1.21, 95% CI 1.09-1.34, PH = 0.522), while the homozygote model gave a 47% increased risk for CAD in Asian population (OR = 1.47, 95% CI 1.21-1.78, PH = 0.314). CONCLUSIONS Our results indicated that the NFKB1-94ins/del ATTG polymorphism was associated with susceptibility to CAD in both Asian and Caucasian populations.

Mean platelet volume to platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection.

Type A acute aortic dissection is a life-threatening vascular emergency because of its high morbidity and mortality. Platelet is a pivotal ingredient involved in the development of acute aortic dissection. In this study, we aimed to investigate whether mean platelet volume (MPV)/platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection. In this single-center and prospective cohort study, 106 consecutive patients with Stanford type A acute aortic dissection admitted to the hospital within 12 h after onset were recruited. The best cut-off value of MPV/platelet count ratio predicting all-cause mortality was determined by the receiver operator characteristic analysis. Patients were divided into high (H-MPV/platelet count) and low (L-MPV/platelet count) groups based on the cut-off value of 7.49 (102 fl/109/l). Patients were followed up for 3.5 years. Of the 106 acute aortic dissection patients, 71 (67.0%) died during the study period, with a median follow-up duration of 570 days. Compared to the L-MPV/platelet count group, patients with H-MPV/platelet count had a higher risk of in-hospital complications including hypotension, hypoxemia, myocardial ischemia/infarction, conscious disturbance, pericardial tamponade, paraplegia, and poor survival (all P < 0.05). In multivariable Cox regression models adjusted for potential confounders, MPV/platelet count ratio was positively associated with the hazard of all-cause mortality, irrespective of interventions either with medication only or urgent surgery, and the hazard ratios were 2.81 (95% confidence interval 1.28–4.48) for the H-MPV/platelet count group when taking L-MPV/platelet count group as the reference (P = 0.005). The MPV/platelet count ratio was a strong independent predictor for in-hospital complications and long-term mortality in patients with type A acute aortic dissection.

Usefulness of plasma matrix metalloproteinase-9 levels in prediction of in-hospital mortality in patients who received emergent percutaneous coronary artery intervention following myocardial infarction

The aim of the present study was to investigate the predictive value of the plasma matrix metalloproteinase-9 (MMP-9) level at admission for in-hospital mortality in patients who received emergency percutaneous coronary intervention (PCI) following AMI. A single blood sample was collected at admission from 155 consecutive AMI patients who underwent emergent PCI. The plasma levels of MMP-9 value (528.9±191.6 ng/ml) were significantly higher in the patients who died (n=24) than in the survivors (385.4±236.0 ng/ml) during 14 days of hospitalization (P=0.005). The age, left ventricle wall motion score index (WMIS), Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) levels and GENSINI score at admission were significantly different between the patients who died and those who survived (P<0.001, P=0.004, P<0.001 and P<0.001, respectively). Cut-off concentrations for prediction of death was identified from receiver operator characteristic (ROC) curves. Using the cut-off value (MMP-9 level 398.2 ng/ml) to stratify the patients into two groups, the group with higher MMP-9 levels had a greater rate of in-hospital mortality than the lower level group (P<0.001). With the exception of the GRACE score, among all biomarkers measured, in stepwise multiple logistic regressions, only the MMP-9 level predicted the risk of in-hospital death after adjustment for all other risk factors (odds ratio 5.02, 95% CI 1.44 to 17.55). In conclusion, a higher MMP-9 level is an independent predictor of in-hospital death in AMI patients who received emergency PCI.

Recombinant adeno-associated virus serotype 9 in a mouse model of atherosclerosis: Determination of the optimal expression time in vivo

Adeno-associated virus 9 (AAV9) has been identified as one of the optimal gene transduction carriers for gene therapy. The aim of the present study was to determine the gene transfection efficiency and safety of an AAV9 vector produced using a recombinant baculovirus (rBac)-based system. AAV9-cytomegalovirus (CMV)-green fluorescent protein was produced using an rBac system and the resulting vector particles were injected intravenously into mice. Animals were sacrificed at 14, 21, 28, 35, 60, 90 and 120 days following injection. GFP expression in aortic vasculature and aortic plaques in C57/6B and apolipoprotein E−/− mice was analyzed by fluorescence imaging and western blotting. In vivo analyses of biological markers of liver and heart damage, and renal function, as well as in vitro terminal deoxynucleotidyl transferase dUTP nick end labeling analysis were used to determine the toxicity of the AAV9 carrier. The findings of the present study demonstrated that AAV9 viral vectors packaged using the rBac system functioned appropriately in arteriosclerosis plaques. The CMV promoter significantly induced GFP expression in the vascular plaque in a time-dependent manner. AAV9-CMV viral particles did not lead to heart, liver or renal damage and no change in apoptotic rate was identified. These findings indicated that AAV9-CMV may be effectively and safely used to transfect genes into atherosclerotic plaques.