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Wang E.,Peking Union Medical College | Wang Z.,Peking Union Medical College | Liu S.,Peking Union Medical College | Gu H.,Peking Union Medical College | And 13 more authors.
Molecular Biology Reports | Year: 2014

Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-β1 (TGFβ1), TGFβ receptor II (TGFβR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFβ1 rs1800469 C>T, TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFβ1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95 % confidence interval (CI) = 0.30-0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95 % CI 0.28-1.00). In stratification analyses, the TGFβ1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95 % CI 0.22-0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95 % CI 0.24-0.83). Our findings suggest that TGFβ1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects. © 2014 Springer Science+Business Media. Source


Gong D.,Chinese Academy of Sciences | Gu H.,Chinese Academy of Sciences | Gu H.,Jiangsu University | Zhang Y.,Wenzhou Medical College | And 7 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2012

Background: Folic acid has an important role during embryo logic development, particularly the development of the cardio vascular system. Methods: We analyzed the involvement of eight polymorphisms in genes related to folic-acid metabolism, 5,10-methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), transcobalamin (TCN2), reduced folate carrier (RFC), nicotinamide-N-methyltransferase (NNMT) and natriuretic peptide precursor A (NPPA) as risk factors of conotruncal heart defects. Results: In single-locus analyses, the genotype frequencies of MTHFR rs1801133 C> T were 18.4% (CC), 50.4% (CT), and 31.1 % (TT) in the subjects with conotruncal heart defects and 31.6 % (CC), 52.9 % (CT), and 15.4 % (TT) in control subjects, and the difference was significant (p=0.001). Logistic regression analyses revealed that, if the MTHFR rs1801133 CC homozygote genotype was used as the reference group, subjects carrying the TT variant homozygote had a significant 3.46-fold [odds ratio (OR) 3.46;95 % confidence interval (CI) 1.83-6.55] increased risk of conotruncal heart defects. If the RFC rs1051266 GG homozygote genotype was used as the reference group, subjects carrying the GA variant heterozygote had a significant 1.68-fold (OR 1.68;95 % CI 1.02-2.78) increased risk of conotruncal heart defects. In stratification analyses, the MTHFR rs1801133 C>T genotype was associated with an increased risk for tetralogy of Fallot (TOF) and transposition of great artery (TGA) in homozygote comparisons, the dominant genetic model, and the recessive genetic model. The RFC rs1051266 GA genotype was associated with an increased risk for TGA compared with wild-type homozygotes and, in the dominant genetic model, the RFC rs1051266 GA/AA genotype was also associated with a significantly increased risk of TGA compared with RFC rs1051266 GG genotypes. Conclusions: These data suggest that genotypes for the MTHFR C677T and RFC rs1051266 polymorphism might be associated with the risk of conotruncal heart defects. © 2012 by Walter de Gruyter • Berlin • Boston. Source


Wang W.,Peking University | Zhao Y.,Peking University | Yang J.,Peking University | Lin B.,Peking University | And 3 more authors.
Molecular Biology Reports | Year: 2013

Cyclin D1 (CCND1) plays a critical role in the G1 to S-phase cell cycle transition. Data on the association between the CCND1 A870G polymorphism and oral cancer are conflicting. To assess the relationship between the CCND1 A870G genotype and the risk of developing oral cancer, we performed a meta-analysis. We searched PubMed to December 1, 2011, for studies on this topic that had been published in the English. For each study, we calculated odds ratios (ORs) and 95% confidence intervals (CIs), assuming the frequency of allele comparison, homozygote comparison, recessive and dominant genetic models. We then calculated pooled ORs and 95% CIs. Seven studies were included in the meta-analysis. The CCND1 G allele was not associated with oral cancer in the frequency of allele comparison (G vs. A: OR=0.882; 95% CI=0.684-1.137; p=0.001 for heterogeneity). In the subgroup analysis, the CCND1 G allele was associated with a borderline significantly decreased risk of developing oral cancer in Asians in the frequency of allele comparison (G vs. A: OR=0.800; 95% CI=0.636-1.006; p=0.089 for heterogeneity), and the association between the GG genotype and oral cancer was significant in Asians with respect to both the homozygote comparison (GG vs. AA: OR=0.644; 95% CI=0.491-0.843; p=0.186 for heterogeneity) and the dominant genetic model (GG+AG vs. AA: OR=0.713; 95% CI=0.584-0.870; p=0.293 for heterogeneity). Our analysis provides evidence that genotypes for the CCND1 A870G polymorphism may be associated with an increased risk of developing oral cancer in the Asian population. © 2012 Springer Science+Business Media Dordrecht. Source


Gao P.,Peking Union Medical College | Gao P.,Research Center for Cardiovascular Regenerative Medicine | Xiong H.,Peking Union Medical College | Zheng Z.,Peking Union Medical College | And 5 more authors.
Platelets | Year: 2010

"One-stop" hybrid coronary revascularization has emerged to be a reliable and attractive alternative for selected patients with multivessel coronary artery disease. However, the optimal antiplatelet regimen of the one-stop hybrid procedure still remains controversial. We modified the antiplatelet protocol in order to reduce the risk of perioperative bleeding and maximally inhibit platelet activity. This study sought to investigate whether the inhibition of platelet activity by this modified antiplatelet protocol is comparable with the conventional protocol widely used and recommended in percutaneous coronary interventions (PCI). Twenty three patients undergoing one-stop hybrid procedure and 20 patients undergoing conventional PCI were enrolled in this prospective study. The modified antiplatelet protocol included perioperative use of aspirin; clopidogrel was administered immediately before PCI with a 300 mg loading dose, followed by a maintenance dose of 75 mg/day for 12 months. Blood samples were obtained before the operation and 2 hours, day 1 and day 3 after operation. Platelet aggregation was induced with: 1) arachidonic acid (AA) (final concentration 0.5 mmol/L) to assess the efficacy of aspirin; 2) adenosine diphosphate (ADP) (final concentration 10 mol/L) to assess the specific efficacy of clopidogrel. Platelet counts were statistically lower in the hybrid group than in the PCI control group (p=0.0018) on day 1 after operation. AA-induced platelet aggregation increased significantly in comparison with the preoperative baseline values (p=0.0079) and the PCI control group (p=0.0023) on day 1 after operation. ADP-induced platelet aggregation gradually decreased in the hybrid group, and achieved similar platelet inhibition with the PCI group on 2 hours and day 1 after operation. No major adverse clinical events such as death, perioperative myocardial infarction, stent thrombosis or reoperation for bleeding occurred in both groups within 30 days after procedure. These results demonstrate that our modified antiplatelet therapy can sufficiently inhibit platelet activity similarly as the conventional protocol for PCI early after operation. Thus, this modified protocol, with continuous use of aspirin and intraoperative administration of loading dose clopidogrel, might be a safe and effective antiplatelet strategy for the one-stop hybrid coronary revascularization. © 2010 Informa Healthcare Ltd. Source


Xin Y.,Chinese Academy of Sciences | Xin Y.,Research Center for Cardiovascular Regenerative Medicine | Wang Y.-M.,Research Center for Cardiovascular Regenerative Medicine | Wang Y.-M.,Chinese PLA General Hospital | And 7 more authors.
Artificial Organs | Year: 2010

Our aim was to study the aging effects on the in vitro biological properties of bone marrow-derived mesenchymal stem cells (BMSCs) for construction of tissue-engineered heart valves. BMSCs were taken from teenagers with congenital heart diseases, and middle-aged and elderly patients with valvular diseases. Proliferative abilities were compared among the three groups by using colony-forming unit counting and growth curves (5-bromo-2′- deoxyuridine assay). Cell differentiation, vascular endothelial growth factor (VEGF) release under hypoxic condition, and migratory abilities were compared as well. Colony-forming units in the teenage group were significantly greater than those in the other two groups (P < 0.05), and significantly higher counts were observed in the middle age group than in the aged group (P < 0.05). Growth curves presented similar trends in which cells' proliferative abilities in the aged group decreased significantly (P < 0.05), while no differences were noted between the two nonaged groups. The differentiation potential to endothelial cells, osteoblasts and adipocytes, VEGF releases, and migratory abilities differed significantly between the aged group and nonaged groups (P < 0.05). However, no differences were noted between the two nonaged groups. BMSCs from older patients with heart valve diseases could be harvested and expanded successfully, and the phenotype and morphology were uniform as nonaged groups. However, the proliferative and differentiation properties of aged cells, as well as cytokine release and migratory abilities, are significantly impaired. Source

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