Coronary heart disease (CHD) related genes and targets, as well as drug targets for preventing and treating CHD were taken as the study objects to build a CHD disease network and a drug action network preventing and treating CHD. Such topological characteristic parameters of the networks as degree distribution, characteristic path length, connectivity and heterogeneity were analyzed to verify the reliability of the networks. On that basis, the intersection calculation was conducted for both networks to analyze the drug action mechanism of their sub-networks. The disease network are composed of 15,221 nodes and 31,177 sides, while the drug action network preventing and treating CHD has 15,073 nodes and 32,376 sides. Both of their topological characteristic parameters showed scale-free small world structural characteristics. Two reaction pathways in the sub-networks-calcitonin gene-related peptide and IL-6 activated JAK/STAT were taken as examples to discuss the indirect action mechanism for preventing and treating CHD. The results showed that the biological network analysis method combining the disease network and the drug action network is helpful to further studies on the action mechanism of the drugs, and significant to the prevention and treatment of diseases.
Computational Biology ; Coronary Artery Disease ; drug therapy ; genetics ; pathology ; prevention & control ; Databases, Genetic ; Humans ; Molecular Targeted Therapy ; Signal Transduction ; drug effects

OBJECTIVETo investigate the expression of myeloid-related protein complex (MRP-8/14) in children with acute Kawasaki Disease (KD).

METHODSA total of 41 children with acute KD and 40 age- and sex-matched control children with upper respiratory tract infection were recruited. Serum levels of MRP-8/MRP-14 complex were measured by ELISA, messenger ribonucleic acid (mRNA) abundance of MRP-8 and MRP-14 in circulating granulocytes and monocytes was determined by RT-PCR, and the number of circulating endothelial cells was determined by flow cytometry.

RESULTSWhen the analysis was stratified according to the presence or absence of coronary artery ectasia in the KD patient group, serum levels of MRP-8/MRP-14 complex, MRP-8 and MRP-14 mRNA abundance in granulocytes, and the number of circulating endothelial cells were all significantly higher in KD patients with coronary artery ectasia than in KD patients without coronary artery ectasia (P<0.05). Serum levels of MRP-8/MRP-14 complex were positively correlated with the number of endothelial cells in the circulation (r=0.69, P<0.05).

CONCLUSIONSSerum levels of MRP-8/MRP-14 complex are elevated in a positive association with the number of circulating endothelial cells in KD children with coronary artery ectasia, suggesting a causative role in the development of coronary artery lesions.

Acute Disease ; Calgranulin A ; blood ; genetics ; physiology ; Calgranulin B ; blood ; genetics ; physiology ; Child, Preschool ; Coronary Artery Disease ; etiology ; Endothelial Cells ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; pathology ; RNA, Messenger ; analysis

BACKGROUND: The heme oxygenase-1 gene (HMOX1) promoter polymorphisms modulate its transcription in response to oxidative stress. This study screened for HMOX1 polymorphisms and investigated the association between HMOX1 polymorphisms and coronary artery disease (CAD) in the Korean population. METHODS: The study population consisted of patients with CAD with obstructive lesions (n=110), CAD with minimal or no lesions (n=40), and controls (n=107). Thirty-nine patients with CAD with obstructive lesions underwent follow-up coronary angiography after six months for the presence of restenosis. The 5'-flanking region containing (GT)n repeats of the HMOX1 gene was analyzed by PCR. RESULTS: The numbers of (GT)n repeats in the HMOX1 promoter showed a bimodal distribution. The alleles were divided into two subclasses, S25 and L25, depending on whether there were less than or equal to and more than 25 (GT)n repeats, respectively. The allele and genotype frequencies among groups were statistically not different. More subjects in the S25-carrier group had the low risk levels of high sensitivity C-reactive protein (hsCRP) for the CAD than those in the non-S25 carrier group (P=0.034). Multivariate logistic regression analysis revealed that the genotypes of (GT)n repeats were not related to CAD status. The restenosis group in the coronary angiography follow-up did not show any significant difference in HMOX1 genotype frequency. CONCLUSIONS: The HMOX1 genotypes were not found to be associated with CAD, but the short allele carrier group contained more individuals with hsCRP values reflecting low risk of cardiovascular disease in the Korean population.
5' Untranslated Regions ; Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; C-Reactive Protein/analysis ; Coronary Angiography ; Coronary Artery Disease/*genetics/pathology ; Coronary Restenosis/complications/therapy ; Dinucleotide Repeats/genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Heme Oxygenase-1/*genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Republic of Korea ; Risk Factors

Aortic Valve Stenosis ; blood ; diagnosis ; etiology ; Child ; Coronary Artery Disease ; blood ; diagnosis ; etiology ; Coronary Vessels ; diagnostic imaging ; pathology ; Echocardiography ; Female ; Humans ; Hyperlipoproteinemia Type II ; blood ; complications ; diagnosis ; genetics ; Lipoproteins, LDL ; blood ; Triglycerides ; blood

OBJECTIVETo assess the association of TLR4 gene polymorphisms with large artery atherosclerosis (LAA) stroke and liability to atherosclerosis in an ethnic Han population from northern China.

METHODSThe study has involved 286 LAA stroke patients and 300 healthy controls. The LAA group has been divided 4 subsets according to angiostenosis conditions. Polymerase chain reaction-restriction fragment length polymorphism and pyrosequencing were employed to analyze three single nucleotide polymorphism (SNPs) (rs1927914, rs1927911 and rs2149356) of the TLR4 gene. A Haploview software package was used to analyze the haplotypes.

RESULTSSNPs rs1927911 and rs2149356 were associated with LAA stroke. Genotypic and allelic frequencies of rs1927914 did not differ significantly between the two groups. Genetic variants of the three SNPs did not vary significantly between all subsets. Haplotype analysis was revealed a significant difference between the LAA group and the control group. Compared with the controls, the frequencies of haplotypes H2 and H8 were lower, and that of H3 was greater in the LAA group.

CONCLUSIONAn association between the TLR4 gene polymorphisms and LAA stroke subtype in ethnic Han population in northern China has been found. However, no association of liability to atherosclerosis in different vascular bed has been found with these polymorphisms.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Coronary Artery Disease ; ethnology ; genetics ; pathology ; Coronary Vessels ; pathology ; Female ; Genetic Association Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Stroke ; ethnology ; genetics ; pathology ; Toll-Like Receptor 4 ; genetics

OBJECTIVETo investigate the association of the ATP-binding cassette sub-family G member 1 (ABCG1) gene polymorphisms with coronary atherosclerotic disease (CAD) in Chinese Han population.

METHODSA population based case-control association study was carried out in 541 patients with CAD and 649 healthy controls from Chinese Han population. Two single nucleotide polymorphisms (SNPs) of the ABCG1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression was used to compare the genotypic and allelic frequency difference.

RESULTSThe frequency of allele C of rs225374 was significantly higher in the CAD patients than that in the healthy controls (OR=1.186, 95%CI: 1.009-1.394, P=0.039), while the difference was also significant in the male subgroup (OR=1.236, 95%CI: 1.014-1.506, P=0.036). A statistically higher frequency of rs1044317 allele A was found in the CAD patients in comparison to the healthy controls (OR=1.187, 95%CI: 1.009-1.397, P=0.039). In case-only association study, rs225374 showed significant association in the high Gensini score group compared with the low Gensini score group (OR=1.303, 95%CI: 1.024-1.657, P=0.031).

CONCLUSIONThe two SNPs of the ABCG1 gene might be associated with the susceptibility and severity of CAD in Chinese Han population.

ATP Binding Cassette Transporter, Sub-Family G, Member 1 ; ATP-Binding Cassette Transporters ; genetics ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; Coronary Artery Disease ; ethnology ; genetics ; pathology ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide