Longxian Cheng

Huazhong University of Science and Technology, Wu-han-shih, Hubei, China

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Publications (31)146.29 Total impact

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    ABSTRACT: Background: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data on smoking in Chinese is limited. Objectives: We aimed to investigate epigenome-wide methylation in relation to smoking in Chinese. Methods: We measured the methylation levels at >485,000 CpGs of blood leukocytes using HumanMethylation450 BeadChip and conducted a genome-wide meta-analysis of smoking in a total of 596 Chinese participants. For the smoking-related CpGs, we further evaluated their associations with internal polycyclic aromatic hydrocarbons (PAHs) biomarkers and their correlations with the expression of corresponding genes. Results: We identified 318 CpGs whose methylation levels were associated with smoking at genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs were significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAHs biomarker for smoking. Conclusion: We identified DNA methylation markers associated with smoking in Chinese populations, including some that also were correlated with gene expression. Exposure to naphthalene, a by-product of tobacco smoke, may contribute to smoking-related methylation.
    No preview · Article · Jan 2016 · Environmental Health Perspectives
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    ABSTRACT: Abnormal expression of thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR) was found in patients with acute coronary syndrome. Ticagrelor, an oral platelet ADP P2Y12 receptor antagonist, is widely used in these patients. The aim of this study was to verify whether different doses of ticagrelor regulated plaque progression and platelet activity by modulating TSLP/TSLPR. Seventy-five ApoE-/- mice were randomly divided into five groups: (1) high-cholesterol diet (HCD, n = 15); (2) HCD plus ticagrelor 25 mg/kg/d (T1, n = 15); (3) HCD plus ticagrelor 50 mg/kg/d (T2, n = 15); (4) HCD plus ticagrelor 100 mg/kg/d (T3, n = 15); and (5) a normal diet group (ND, n = 15). At day 0 and at week 16, blood lipids and serum TSLP levels, expression of TSLPR, CD62, and CD63, platelet aggregation, platelet ATP release, PI3K/Akt signaling pathway, and plaque morphology were assessed. HCD increased TSLPR expression and atherosclerosis progression but high-dose ticagrelor (100 mg/kg) moderated this trend. TSLPR was positively correlated with Akt1, platelet aggregation, corrected plaque area, and vulnerability index in the T3 group (P<0.01). In conclusion, low-dose ticagrelor only inhibited platelet activity. Besides this inhibition, high-dose ticagrelor modulated platelet activity and atherosclerosis mediated by TSLPR, potentially through the PI3K/Akt signal pathway.
    Preview · Article · Oct 2015 · PLoS ONE
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    ABSTRACT: Ageing is related to the risk of many diseases and is affected by genetic, epigenetic, and environmental factors. Exposure to the ubiquitous pollutant polycyclic aromatic hydrocarbons (PAHs) is known to cause health damage, but the relation between such exposure with methylation ageing has not been studied. We undertook an association analysis of exposure to PAHs and DNA methylation ageing, a novel and promising ageing marker.
    No preview · Article · Oct 2015 · The Lancet
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    ABSTRACT: Impaired glucose regulation (IGR), containing prediabetes and diabetes, is an inflammatory disease. The interleukin-33 (IL-33)/IL-1 receptor-like 1 and IL-1/IL-1 receptor (IL-1R) pathways are involved and play opposite roles. While the IL-1R-associated protein (IL-1Rap) is indispensible for the two pathways, the association between the single-nucleotide polymorphisms (SNPs) of the IL-1Rap gene and IGR has not been determined. TaqMan probe quantitative polymerase chain reaction was used to genotype 11 SNPs in the regions of the IL-1Rap gene selected on the basis of linkage disequilibrium using the HapMap database in a study of 889 individuals (156 IGR patients in the case group and 733 non-diabetic patients in the control group). Logistic regression was applied to control the potential confounders in the multivariate analysis. Among 11 SNPs, IL-1Rap rs3773958 was associated with IGR. Further analysis showed that the odds ratios for GT and GT + GG carriers vs. TT carriers were 1.686 and 1.669, respectively, adjusted for gender, age, weight, waist, drinking, smoking, hypertension, alanine aminotransferase, total cholesterol and triglycerides. For rs3773958 in the non-smoking subgroup, GT and GT + GG carriers had a significantly higher risk of IGR compared to the TT carriers. The same conclusions were drawn using data from non-drinking and non-overweight subgroups. However, interactions between rs3773958 and smoking, drinking or being overweight were not significant. In conclusion, rs3773958 in the IL-1Rap gene region was associated with IGR.
    Preview · Article · Apr 2015
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    ABSTRACT: Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. ELISA determined plasma interleukin-6 (IL6), IL10, IL17A, IFN-γ, and C-reactive protein (CRP) from 476 AAA patients and 200 controls. AAA patients had lower IL6, IFN-γ, IL10, IL17A, and higher CRP than controls. IL10 correlated positively with IFN-γ, IL17A, or IL6, but not CRP in control or AAA populations. IL10 associated negatively with systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-γ, IL17A, and CRP correlated positively with cross-sectional AAA area after adjustment. IL10 correlated positively with AAA growth rate before and after adjustment. The risk of death doubled in AAA patients with CRP levels above the median. Reduced IFN-γ, IL10, and IL17A in AAA patients, positive correlations of IFN-γ and IL17A with cross-sectional AAA area, IL10 with AAA growth rate, and IL10 with IFN-γ and IL17A suggest combined Th1, Th2, and Th17 immune responses in human AAAs.
    No preview · Article · Apr 2015 · Annals of Medicine
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    ABSTRACT: Recently, interleukin (IL)-9 was found to be involved in the pathogenesis of many inflammatory diseases. Here, we tested whether IL-9 was related to atherosclerosis and investigated the underlying mechanisms. IL-9R was expressed in mouse aortic endothelial cells (MAECs) and aortic tissues, and IL-9 levels were elevated in plasma and aortic arches in Apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice fed a Western diet for 10 weeks were administered recombinant mouse IL-9 (rIL-9) or anti-IL-9 neutralizing monoclonal antibody (mAb). Mice treated with rIL-9 developed markedly larger plaques in both the aorta and aortic root. Immunohistochemical studies demonstrated increases in both vascular endothelial adhesion molecule-1 (VCAM-1) expression and the infiltration of inflammatory cells, including T cells and macrophages, in plaques. However, treatment with the anti-IL-9 mAb caused the opposite effect. The administration of rIL-9 did not affect the splenic T cell or peripheral monocyte subsets. Meanwhile, IL-9 induced VCAM-1 expression in MAECs mainly via a STAT3-dependent pathway, consequently increasing monocyte-endothelial adhesion. Moreover, treatment with anti-VCAM-1 mAb partially abrogated the IL-9-induced increase in plaque area. In addition, CD4(+)IL-9(+) T cells and IL-9 were increased in patients with acute coronary syndrome, and the levels of IL-9 in culture supernatants and soluble VCAM-1 (sVCAM-1) in plasma were significantly positively correlated in the enrolled patients. Our results demonstrated that IL-9 exerted pro-atherosclerotic effects in ApoE-/- mice at least partially by inducing VCAM-1 expression, which mediated inflammatory cell infiltration into atherosclerotic lesions. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    Preview · Article · Mar 2015 · Cardiovascular Research
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    ABSTRACT: The IL-33/ST2 signaling pathway plays an important role in coronary artery disease (CHD); however, few studies have explored how variants in IL-33/ST2 genes influence CHD risk. Here, we examined the association between genetic variants in IL-33, ST2, and IL-1RAcP of the IL-33/ST2 axis and the risk of CHD. We conducted a case-controlled study with 1146 CHD cases and 1146 age- and sex-frequency-matched controls. Twenty-eight single nucleotide polymorphisms (SNPs) in IL-33, ST2, and IL-1RAcP were genotyped by Sequenom MassArray and TaqMan assay. Logistic regression was used to analyze these associations. The SNP rs4624606 in IL-1RAcP was nominally associated with CHD risk. The AA genotype was associated with a 1.85-fold increased risk of CHD (95% confidence interval (CI) = 1.01-3.36; p = 0.045) compared to the TT genotype. Further analysis showed that AA carriers also had a higher risk of CHD than TT + TA carriers (odds ratio (OR) = 1.85; 95% CI = 1.85-3.35; p = 0.043). However, no significant association was observed between variants in IL-33/ST2 genes and CHD risk. Further studies are needed to replicate our results in other ethnic groups with larger sample size.
    Full-text · Article · Dec 2014 · International Journal of Molecular Sciences
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    ABSTRACT: -Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. -In the discovery stage, the plasma of 20 AMI patients and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 AMI patients and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays, and further replicated in 150 AMI patients and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in AMI patients than controls in both validation populations (p<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio [OR] 4.71, 95% confidence interval [CI] 2.96 to 7.48; OR 4.27, 95% CI 2.84 to 6.41, respectively). Addition of the two miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% CI, 0.787-0.856) to 0.871 (95% CI, 0.842-0.900), with a net reclassification improvement of 20.45% (p<0.0001) and an integrated discrimination improvement of 0.16 (p<0.0001) for AMI patients. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for CHD in human vascular endothelial cells. -The plasma levels of miR-320b and miR-125b were significantly lower in AMI patients compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.
    Full-text · Article · Mar 2014 · Circulation Cardiovascular Genetics
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    ABSTRACT: Aims: Studies indicated that body iron stores were associated with coronary heart disease (CHD). Type 2 transferrin receptor (TFR2) participates in cellular iron overload and is related to cardiovascular disease. No studies investigated the associations between variants in TFR2 gene and CHD risk. Methods: We sought to investigate this association in a Chinese Han population and performed a case-control study recruiting 1264 CHD patients and 1264 age and sex frequency matched controls. TaqMan single nucleotide polymorphisms (SNP) allelic discrimination was used to examine genotypes of the tagging single nucleotide polymorphisms (tagSNPs) of TFR2. The plasma ferritin levels were measured by ELISA. Results: We did not find significant associations between variants of TFR2 gene (including tagSNPs rs2075674 and rs7385804) and the risk of CHD. After adjustment for the conventional risk factors of CHD, such as smoking and age, the results did not materially alter. Interaction analyses indicated that there were no significant interactions between conventional risk factors of CHD and these two tagSNPs on CHD risk. Among different genotypes of these two tagSNPs, no significant differences in plasma ferritin levels were found. Conclusion: In summary, the variants of rs2075674 and rs7385804 in TFR2 gene were not associated with CHD risk in a Chinese Han population.
    No preview · Article · Jun 2013 · Journal of Cardiovascular Medicine
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    ABSTRACT: Mutations in SCN5A, the gene encoding the pore-forming subunit of cardiac Na+ channels, cause a spectrum of arrhythmic syndromes. Of these, sinoatrial node (SAN) dysfunction occurs in patients with both loss- and gain-of-function SCN5A mutations. We explored for corresponding alterations in SAN function and intracardiac conduction and clarified possible mechanisms underlying these in an established mouse long QT syndrome type 3 model carrying a mutation equivalent to human SCN5A-ΔKPQ. Electrophysiological characterizations of SAN function in living animals and in vitro sinoatrial preparations were compared with cellular SAN and two-dimensional tissue models exploring the consequences of Scn5a+/ΔKPQ mutations. Scn5a+/ΔKPQ mice showed prolonged electrocardiographic QT and corrected QT intervals confirming long QT phenotypes. They showed frequent episodes of sinus bradycardia, sinus pause/arrest, and significantly longer sinus node recovery times, suggesting compromised pacemaker activity compared with wild-type mice. Electrocardiographic waveforms suggested depressed intra-atrial, atrioventricular node, and intraventricular conduction in Scn5a+/ΔKPQ mice. Isolated Scn5a+/ΔKPQ sinoatrial preparations similarly showed lower mean intrinsic heart rates and overall slower conduction through the SAN to the surrounding atrium than did wild-type preparations. Computer simulations of both single SAN cells as well as two-dimensional SAN-atrial models could reproduce the experimental observations of impaired pacemaker and sinoatrial conduction in terms of changes produced by both augmented tail and reduced total Na+ currents, respectively. In conclusion, the gain-of-function long QT syndrome type 3 murine Scn5a+/ΔKPQ cardiac system, in overlap with corresponding features reported in loss-of-function Na+ channel mutations, shows compromised SAN pacemaker and conduction function explicable in modeling studies through a combination of augmented tail and reduced peak Na+ currents.
    No preview · Article · Jan 2012 · AJP Heart and Circulatory Physiology
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    ABSTRACT: Although (GT) n repeats in heme oxygenase-1 (HO-1) promoter may modulate gene transcriptional activity, the association between (GT) n repeats polymorphism and risk of coronary heart disease (CHD) from different levels of oxidative stress (OS) is unknown. We determined the allelic frequencies of (GT) n repeats in the HO-1 gene promoter and plasma malonaldehyde (MDA) as biomarkers of OS in 2,298 pairs of CHD patients and controls in the Chinese population. Furthermore, we measured MDA in culture mediums and HO-1 expressions levels in cell lysates of endothelial cells carrying various (GT) n genotypes under different concentrations of H2O2. Compared with L/L genotype (>25 repeats) carriers, the adjusted odd ratios for S/S genotype (≤25 repeats) in subjects with different levels of OS (MDA < 1.83, 1.83–2.91, >2.91 μmol/L) were 1.06 (95%CI, 0.75 to 1.49), 0.79 (95%CI, 0.55 to 1.12), and 0.60 (95%CI, 0.44 to 0.81), respectively (P interaction = 0.002). In biological experiments, compared with endothelial cells carrying L/L genotype, cells with S/S genotype did not have a significantly higher HO-1 expression under 0 μmol/L H2O2, but displayed a significantly higher HO-1 expression under 50 μmol/L H2O2 (P interaction = 0.003). S/S genotype in HO-1 gene promoter is associated with a lower risk of CHD in subjects with higher levels of OS, because under conditions of high OS, the S/S genotype has higher levels of HO-1, an antioxidant.
    Full-text · Article · Nov 2011 · Cell Stress and Chaperones
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    ABSTRACT: Recent genome-wide association studies (GWAS) have mapped several novel loci influencing blood lipid levels in Caucasians. We sought to explore whether the genetic variants at newly identified lipid-associated loci were associated with CHD susceptibility in a Chinese Han population. We conducted a two-stage case-control study in a Chinese Han population. The first-stage, consisting of 1,376 CHD cases and 1,376 sex and age- frequency matched controls, examined 5 novel lipid-associated single-nucleotide polymorphisms (SNPs) identified from GWAS among Caucasians in relation to CHD risk in Chinese. We then validated significant SNPs in the second-stage, consisting of 1,269 cases and 2,745 controls. We also tested associations between SNPs within the five novel loci and blood lipid levels in 4,121 controls. We identified two novel SNPs (rs599839 in CELSR2-PSRC1-SORT1 and rs16996148 in NCAN-CILP2) that were significantly associated with reduced CHD risk in Chinese (odds ratios (95% confidence intervals) in the dominant model 0.76 (0.61-0.90; P = 0.001), 0.67 (0.57-0.77; P = 3.4×10(-8)), respectively). Multiple linear regression analyses using dominant model showed that rs599839 was significantly associated with decreased LDL levels (P = 0.022) and rs16996148 was significantly associated with increased LDL and HDL levels (P = 2.9×10(-4) and 0.001, respectively). We identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.
    Full-text · Article · Nov 2011 · PLoS ONE
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    Dataset: Table S1
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    ABSTRACT: Associations between SNPs at newly identified lipid-associated loci with lipid levels in Chinese. (DOC)
    Preview · Dataset · Nov 2011
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    Dataset: Table S2
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    ABSTRACT: Stratification analysis for association between two SNPs genotypes and risk of CHD. (DOC)
    Preview · Dataset · Nov 2011
  • Ke Zhuang · Wencai Zhang · Xiaobo Zhang · Fangqin Wu · Longxian Cheng
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    ABSTRACT: Associations between "lipid-related" candidate genes, blood lipid concentrations and coronary artery disease (CHD) risk are not clear. We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population. The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population. Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95% CI 0.50 to 0.81), after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk (P<0.01) comparing with the major allele G. Individuals with GT genotype had the lowest CHD risk. No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population. SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population. However, it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.
    No preview · Article · Aug 2011 · Journal of Huazhong University of Science and Technology
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    Dataset: Table S2
    Meian He · Huan Guo · Xiaobo Yang · Li Zhou · Xiaomin Zhang · Longxian Cheng · Hesong Zeng · Frank B. Hu · Robert M. Tanguay · Tangchun Wu
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    ABSTRACT: Primers and probes for genotyping 4 TagSNPs in HSPA8 gene. (0.03 MB DOC)
    Preview · Dataset · Mar 2010
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    Dataset: Table S3
    Meian He · Huan Guo · Xiaobo Yang · Li Zhou · Xiaomin Zhang · Longxian Cheng · Hesong Zeng · Frank B. Hu · Robert M. Tanguay · Tangchun Wu
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    ABSTRACT: Primer sequences used in amplification and reporter plasmids construction. (0.03 MB DOC)
    Preview · Dataset · Mar 2010
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    ABSTRACT: There is ample evidence that Hsp70 takes part in the progress of coronary heart disease (CHD). This implies that genetic variants of Hsp70 genes such as HSPA8 (HSC70) gene might contribute to the development of CHD. The present study aimed to investigate whether certain genetic variants of HSPA8 gene are associated with CHD in Han Chinese people. A total of 2006 subjects (1003 CHD cases and 1003 age- and sex- matched healthy controls) were recruited. Genetic variants in the HSPA8 gene were identified by sequencing of the gene in 60 unrelated Chinese. Four tag single nucleotide polymorphisms (tagSNPs) (rs2236659, rs2276077, rs10892958, and rs1461496) were selected and genotyped. The function of the significant SNP was evaluated using luciferase reporter assays in two cell lines. By sequencing the promoter and all exons and introns of the HSPA8 gene, 23 genetic variants were identified. One promoter SNP rs2236659 was associated with susceptibility to CHD. Carriers of the "C" allele of rs2236659 had decreased CHD risk with odds ratio (OR) of 0.78 (95% CI: 0.62, 0.98; P = 0.033) after adjustment for conventional risk factors. Haplotype analyses indicated that haplotype GCGC contributed to a lower CHD risk (OR = 0.78, 95% CI: 0.65, 0.93; P = 0.006) compared with the common haplotype AGGT. In a transfection assay, the C allele of rs2236659 showed a 37-40% increase in luciferase expression of the reporter gene luciferase in endothelial and non-endothelial cells compared with the T allele. These findings suggest that genetic variants in HSPA8 gene (especially promoter SNP rs2236659) contribute to the CHD susceptibility by affecting its expression level.
    Full-text · Article · Mar 2010 · PLoS ONE
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    Dataset: Table S1
    Meian He · Huan Guo · Xiaobo Yang · Li Zhou · Xiaomin Zhang · Longxian Cheng · Hesong Zeng · Frank B. Hu · Robert M. Tanguay · Tangchun Wu
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    ABSTRACT: Primers and PCR conditions for sequencing HSPA8 gene. (0.06 MB DOC)
    Preview · Dataset · Mar 2010
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    ABSTRACT: Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.
    Full-text · Article · Mar 2010 · Cell Stress and Chaperones