RESUMO
Sour or wild jujube fruits and dried seeds are popular food all over the world. In this study, we reported a high-quality genome assembly of sour jujube (Ziziphus jujuba Mill. var. spinosa), with a size of 406 Mbp and scaffold N50 of 30.3 Mbp, which experienced only γ hexaploidization event, without recent genome duplication. Population structure analysis identified four jujube subgroups (two domesticated ones, i.e., D1 in West China and D2 in East/SouthEast China, semi-wild, and wild), which underwent an evolutionary history of a significant decline of effective population size during the Last Glacial Period. The respective selection signatures of three subgroups were discovered, such as strong peaks on chromosomes #3 in D1, #1 in D2, and #4 in wild. Genes under the most significant selection on chromosomes #4 in wild were confirmed to be involved in fruit variations among jujube accessions, in transcriptomic analysis. Our study offered novel insights into the jujube population structure and domestication and provided valuable genomic resources for jujube improvement in stress response and fruit flavor in the future.
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OBJECTIVE: To explore the polymorphism of cholesteryl ester transfer protein (CETP) gene -629C/A among the coronary heart disease (CHD) Han population of Tianjin area and evaluate the influences of genetic factors on atorvastatin therapeutic effects and clinical outcomes in pharmacogenomics and provide theoretical rationales for individualized treatment. METHODS: A total of 332 angiographically confirmed CHD patients at Tianjin Chest Hospital were recruited from October 2010 to July 2011. The CETP gene promoter polymorphism at position -629 was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). The serum level of CETP was determined by enzyme-linked immunosorbent assay (ELISA).Lipid levels were determined at baseline and 12 months post-treatment with 20 mg/d atorvastatin in all patients. Clinical follow-up were performed for more than 1 year (range, 12-23 months). And major adverse cardiac events (MACE, including death, non-fatal infarction, revascularization and stroke) were analyzed. The Kaplan-Meier Log-rank test was used to compare MACE-free survival between different genotypes. RESULTS: (1) The frequencies of variant -692A allele was 0.476, AA genotype showed reduced CETP levels and higher HDL-C levels compared with CC and CA genotypes. But it did not reach statistical significance (F = 0.893, P = 0.411 and F = 1.279, P = 0.282 respectively). Although a negative trend correlation existed between serum levels of HDL-C and CETP, it did not reach statistical significance (r = -0.151, P = 0.081) . (2) After 12-month therapy of atorvastatin, CC genotype was shown to be associated with higher LDL-C, LP(a) reduction and HDL-C elevation in response to atorvastatin compared with CA and AA genotype.LDL-C levels decreased 43.5% in CC homozygotes, 25.5% in CA heterozygotes and 11.7% in AA homozygotes (P = 0.001).HDL-C levels increased 9.2% in CC homozygotes, 6.8% in CA heterozygotes and 5.5% in AA homozygotes.However the changes of HDL-C levels in three genotypes showed no significant difference (P = 0.412). (3) There was a 7.83% incidence of MACE after a mean follow-up of (18.66 ± 5.99) months. The outcomes were death (n = 3, 0.90%), non-fatal infarction (n = 7, 2.11%), revascularization (n = 13, 3.92%) and stroke (n = 3, 0.90%). The cumulative MACE free survival rates were 96.2% , 92.1% and 87.3% in CC, CA and AA genotypes respectively (Log-rank P = 0.444). CONCLUSION: Variant AA genotype shows a higher level of HDL-C s and a lowered level of CETP.However CC genotype offers a better benefit of statin therapy associated with lowered levels of LDL-C and LP(a). And the long-term clinical prognosis is not affected among three genotypes.
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Proteínas de Transferência de Ésteres de Colesterol/genética , Doença da Artéria Coronariana/tratamento farmacológico , Variação Genética , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirróis/uso terapêutico , Idoso , Atorvastatina , HDL-Colesterol , Doença da Artéria Coronariana/genética , Ensaio de Imunoadsorção Enzimática , Genótipo , Humanos , Regiões Promotoras Genéticas , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate cholesteryl ester transfer protein (CETP) gene polymorphism -629C/A among Han Chinese patients with coronary heart disease (CHD) in Tianjin region, and to assess the influence of genetic factors on therapeutic effect of atorvastatin and clinical outcome in order to provide a pharmacogenomic basis for personalized treatment. METHODS: From October 2010 to July 2011, 232 patients with angiographically confirmed CHD were recruited. Polymorphism of position -629 of CETP gene promoter was determined with polymerase chain reaction - restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP was determined with enzyme-linked immunosorbent assay (ELISA). Lipid level in all patients was determined at baseline and after 12 months of treatment with 20 mg/d atorvastatin. Clinical follow-up was carried out for more than a year (12-23 months). Major adverse cardiac events including death, non-fatal infarction, revascularization and stroke (MACE) were recorded. A Kaplan-Meier log-rank test was used to compare MACE-free survival for individuals with various genotypes. RESULTS: The frequency of -629A allele was 0.408. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels and higher high-density lipoprotein cholesterol (HDL-C) levels, albeit without statistical significance (F = 0.893, P = 0.411 and F = 1.279, P = 0.282, respectively). There also appeared to be a negative correlation between serum HDL-C and CETP levels, though no statistical significance was detected (r = -0.151, P = 0.081). After 12 months atorvastatin therapy, individuals with CC genotype had greater reduction of low-density lipoprotein cholesterol (LDL-C), reduced LP(a) and elevated HDL-C compared with CA or AA genotypes. LDL-C level has decreased by 35.41% in CC homozygotes, 18.84% in CA heterozygotes and 8.15% in AA homozygotes (P = 0.001). HDL-C level has increased by 14.37% in CC homozygotes, 10.48% in CA heterozygotes and 6.64% in AA homozygotes, respectively. However, above changes did not reach statistical significance (P = 0.470). The incidence of MACE after a mean follow-up of (18.66 ± 5.99) months was 7.76%, which included 2 (0.86%) deaths, 5 (2.16%) non-fatal infarctions, 9 (3.88%) revascularizations and 2 (0.86%) strokes. The cumulative MACE-free survival rates were 92.4%, 85.3% and 65.0% for CC, CA and AA genotypes, respectively (Log-rank P = 0.444). CONCLUSION: Our results suggested that AA variant for the -629A allele of CETP gene had higher HDL-C levels and reduced CETP levels, though patients with CC genotype appeared to have better benefited from statin therapy with reduction in LDL-C and LP(a) levels. Long-term clinical prognosis was however not affected by the 3 genotypes.
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Proteínas de Transferência de Ésteres de Colesterol/genética , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/genética , Ácidos Heptanoicos/uso terapêutico , Polimorfismo de Nucleotídeo Único , Pirróis/uso terapêutico , Adulto , Idoso , Atorvastatina , Proteínas de Transferência de Ésteres de Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the relationship between the -629C/A polymorphism in the promoter region of the CETP gene, serum Levels, lipid metabolism, and coronary heart disease (CHD) among Tianjin Han Chinese population. METHODS: A hospital-based case-control study was conducted in Tianjin Chest Hospital from 2010 October to 2011 October. The subjects underwent angiography were divided into a case group (n = 429) and a control group (n = 275). The CETP gene promoter polymorphism at position -629 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method.The serum CETP levels was determined by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: (1)The lower frequency of -629A allele in Tianjin Han Chinese population was 0.408, significantly lower than that in other domestic and foreign populations (0.479-0.701, P < 0.05). (2) Variant AA genotype showed reduced CETP levels(P > 0.05) and higher HDL-C levels (P < 0.05), compared to wild CC genotype. (3) Although there was a negative trend correlation between serum CETP and HDL-C levels, it did not reach statistical significance(P > 0.05). (4)There were significant differences in the frequencies of CETP gene -629 genotype and allele between the two groups (P < 0.001),carries with CA/AA genotype and A allele showed higher risk of CHD, OR (95%CI) values were 4.627 (3.163-6.769), 8.779 (4.799-16.059) and 3.173 (2.453-4.104) respectively. There was no relationship between CETP-629C/A polymorphism and coronary artery stenosis degree(χ(2) = 3.588, P = 0.166). CONCLUSION: The frequencies of CETP gene -629 genotype and allele in the Tianjin Han Chinese population was significantly different from that in Other domestic and foreign populations. Variant AA genotype, which showed reduced CETP levels and higher HDL-C levels, is paradoxically associated with increased risk of CHD. Thus, CETP gene variation may affect coronary risk apart from the level of HDL-C.
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Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol/sangue , Doença das Coronárias/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Proteínas de Transferência de Ésteres de Colesterol/sangue , Doença das Coronárias/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
BACKGROUND: It has been recently reported that inflammatory mechanisms play an important role in in-stent restenosis (ISR) processes. Inflammatory factors after percutaneous coronary intervention (PCI) for dynamic monitoring can probably predict ISR. Functional polymorphisms in the promoter region of genes coding for inflammatory factors might be important for determining the magnitude of the inflammatory response. Thus, in the present study, we aimed to investigate the serial changes in serum interleukin-6 (IL-6) levels before and after PCI and the relationship between the -572C/G polymorphism in the promoter region of the IL-6 gene and ISR. We also discussed genetic polymorphisms in the inflammatory response to PCI. METHODS: A total of 437 patients who successfully underwent bare metal stent (BMS) implantation with a follow-up angiography were divided into an ISR group (n = 166) and a non-ISR (NISR) group (n = 271). The IL-6 gene promoter polymorphism at position -572 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method. The serum IL-6 levels before and one day, five days and 180 days after PCI were determined by the radioimmunoassay method. RESULTS: ISR patients showed higher IL-6 serum levels than NISR patients before PCI ((324.42 ± 28.14) ng/L vs. (283.22 ± 47.30) ng/L, P < 0.001), and one day post-PCI IL-6 serum levels in the ISR group also showed a significantly higher level than in the NISR group (P < 0.001). Increased IL-6 after PCI persisted at a statistically significant level throughout the study in ISR patients, whereas IL-6 levels had normalized five days after the procedure in NISR patients. One day post-PCI serum IL-6 level was the most accurate marker for diagnosis of ISR, the area under the ROC curve being 0.927 (95%CI 0.878 - 0.977). The cut-off value for IL-6 to predict ISR was over 355.50 ng/L, with a sensitivity of 0.968 and a specificity of 0.865. There were no significant differences in frequencies of -572 genotype and allele between the two groups (P > 0.05). One day post-PCI IL-6 serum levels in patients with the G allele was significantly higher than in patients without the G allele ((366.99 ± 49.37) ng/L vs. (347.20 ± 55.30) ng/L, P < 0.05). In the ISR group, one day post-PCI serum levels of IL-6 in patients with the G allele was also significantly higher than that in patients without the G allele ((405.67 ± 26.56) ng/L vs. (375.69 ± 38.81) ng/L, P < 0.05). Multivariate Logistic regression analysis revealed positive correlations between male gender, one day post-PCI serum levels of IL-6, the pre-PCI degree of stenosis, the length of the target lesion stenosis, and restenosis; and there were negative correlations between the stent diameter, the diameter of the reference vessel before stent implantation and restenosis. CONCLUSIONS: IL-6 is an early post-PCI inflammatory cytokine, and one day post-PCI serum IL-6 level is an independent risk factor for restenosis. The frequencies of IL-6 gene -572 genotype and allele are not different between patients with and without ISR in a Chinese Tianjin Han population, but carrying the IL-6 -572G allele is likely to increase an individual's susceptibility to ISR by promoting serum IL-6 levels.
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Angioplastia Coronária com Balão , Reestenose Coronária/sangue , Reestenose Coronária/genética , Interleucina-6/sangue , Interleucina-6/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the impact of omeprazole on platelet response to clopidogrel and the effect of polymorphisms of CYP2C19 on the antiplatelet effect of clopidogrel. METHODS: Platelet aggregation (PA) was assessed before 300 mg aspirin plus 300 mg loading dose of clopidogrel and after 300 mg aspirin plus 75 mg maintenance dose of clopidogrel 7 days later in 414 patients with acute coronary syndrome who have undergone percutaneous coronary intervention (PCI). Thereafter, gastric mucosal protective drugs were given (omeprazolem 20 mg, n=224 or cimetidine 800 mg, n=190). Fourteen days later, PA was measured again. Genotypes of CYP2C19*2 were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: After taken aspirin and clopidogrel, PA has decreased significantly in both groups. Compared with cimetidine, omeprazole had no significant impact on PA on 7 and 21 days post PCI. Compared with homozygotes or heterozygotes for the wild-type CYP2C19*2, patients with CYP2C19*2 AA genotype had significantly higher PA on 7 and 21 days post PCI (P<0.05). CONCLUSION: No attenuating effect on platelet response to clopidogrel has been observed for Omeprazole. The variant of CYP2C19*2 AA genotype is significantly associated with attenuated response to clopidogrel.
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Hidrocarboneto de Aril Hidroxilases/genética , Omeprazol/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Ticlopidina/análogos & derivados , Adulto , Idoso , Hidrocarboneto de Aril Hidroxilases/metabolismo , Clopidogrel , Citocromo P-450 CYP2C19 , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ticlopidina/farmacologiaRESUMO
OBJECTIVE: To investigate the association between polymorphisms at -14 bp and zinc finger protein(ZNF) sites of ATP-binding cassette transporter A1 (ABCA1) gene promotor and high density lipoprotein-cholesterol (HDL-C) level and coronary heart disease (CHD). METHODS: Polymorphisms of Bme13901 restriction site at -14 bp and an insertion/deletion site of ACCCC in variable number of tandem repeats-zinc finger protein(VNTR-ZNF) of ABCA1 gene were detected using PCR in 260 CHD patients and 220 healthy subjects from a Chinese population in Tianjin. RESULTS: CT genotype was most common in both groups with no differences found in between (P> 0.05). No differences were found in the frequencies of the rare T allele for -14 bp (P> 0.05). For the -14 bp site, subjects with CT/TT genotype had a lower serum mean concentration of HDL-C compared with those with the CC genotype (P< 0.05). Genotypic frequencies of VNTR-ZNF were 6.2% for the inserted form, 43.8% for the deleted form and 50.0% for the inserted/deleted form. No significant difference was found in the distribution of allele and genotype, or in the levels of HDL-C between the two groups (P> 0.05). CONCLUSION: The genotypes at -14 bp of ABCA1 gene are associated with the plasma level of HDL-C. HDL-C levels in T allele carriers were significantly lower (P< 0.05). No association was found between variations in ABCA1 VNTR-ZNF and plasma levels of HDL-C, or between the ABCA1 -14 bp and VNTR-ZNF polymorphisms and susceptibility for CHD.
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Transportadores de Cassetes de Ligação de ATP/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , HDL-Colesterol/metabolismo , Proteínas de Ligação a DNA/genética , Transportador 1 de Cassete de Ligação de ATP , Estudos de Casos e Controles , HDL-Colesterol/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: To evaluate the therapeutic effect of hBNP on rats with chronic heart failure (CHF). METHODS: Thirty CHF rats defined by echocardiography at 12 weeks post abdominal aortic constriction were randomly divided into Ad-hBNP group (2.5 × 10(10) VP/ml NS Ad-hBNP 1 ml/week × 4, n = 14), Ad-Track group (n = 8), placebo group (NS, n = 8), 10 sham-operated rats served as control group. After 4 weeks treatment, cardiac function was evaluated by echocardiography and hemodynamic measurements. Heart weight (HW) and HW/body weight (BW) ratio were determined. RESULTS: IVS, LVPW, LVEDD and LVESD were significantly reduced in the Ad-hBNP group [(2.34 ± 0.29) mm, (2.28 ± 0.18) mm, (6.50 ± 0.42) mm, (3.54 ± 0.59) mm] than those in the Ad-Track group [(2.71 ± 0.35) mm, (3.02 ± 0.85) mm, (7.71 ± 0.83) mm, (4.72 ± 0.80) mm] and in the NS group [(2.78 ± 0.23) mm, (2.83 ± 0.53) mm, (7.34 ± 0.97) mm, (4.55 ± 0.77) mm, all P < 0.05]. The LVEF and LVFS of the Ad-hBNP group [(79.27 ± 7.01)%, (43.38 ± 6.73)%] were significantly higher than in the Ad-Track group [(70.85 ± 4.81)%, (35.72 ± 3.68)%] and in the NS group [(69.67 ± 6.90)%, (34.91 ± 5.10)%, all P < 0.01]. HR [(417.48 ± 32.57) beats/min, (446.85 ± 61.49) beats/min, P < 0.05; (440.83 ± 32.18) beats/min, P < 0.05], LVEDP [(-4.24 ± 4.00) mm Hg (1 mm Hg = 0.133 kPa); (21.99 ± 6.80) mm Hg, P < 0.01; (18.00 ± 12.25) mm Hg, P < 0.01] were significantly decreased and while LVSP [(131.79 ± 15.76) mm Hg; (112.99 ± 32.35) mm Hg, P < 0.05; (117.13 ± 15.26) mm Hg], +dP/dt(max) [(5037.20 ± 430.41) mm Hg/s; (4217.40 ± 1354.15) mm Hg/s, P < 0.05; (4310.50 ± 1293.97) mm Hg/s, P < 0.05] and -dP/dt(max) [(-4382.00 ± 1304.79) mm Hg/s; (-3725.00 ± 791.34) mm Hg/s, P < 0.05; (-3890.00 ± 1043.73) mm Hg/s, P < 0.05]were significantly increased in Ad-hBNP group than in Ad-Track group and NS group (all P < 0.05). HW and HW/BW were also decreased in Ad-hBNP group than in the Ad-Track group and the NS group. CONCLUSION: Exogenous hBNP improved the cardiac function and attenuated remodeling in CHF rats.
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Insuficiência Cardíaca/terapia , Peptídeo Natriurético Encefálico/farmacologia , Adenoviridae/genética , Animais , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Masculino , Peptídeo Natriurético Encefálico/genética , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
OBJECTIVE: To investigate the relationship of interleukin-10 gene (IL-10) polymorphism and the serum IL-10 level with restenosis after percutaneous coronary intervention (PCI) in Tianjin Chinese Han population and study the effect of IL-10 gene polymorphism on serum IL-10 level. METHODS: Four hundred and thirty-seven patients who successfully underwent PCI with a follow-up angiography were divided into a restenosis group (n = 166) and non-restenosis group (n = 271). The IL-10 gene promoter polymorphism at position -592 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meanwhile their serum IL-10 level before and 24 h after PCI was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) There was no significant difference in frequencies of -592 genotypes and alleles between the two groups (P > 0.05); (2) The 24 h post-PCI IL-10 serum level of restenosis group was significantly lower than that of the non-restenosis group [(82.67 ± 35.02) ng/L vs. (95.08 ± 32.26) ng/L, P < 0.05]; (3) The serum level of the A allele carriers (AA+AC) was significantly lower than that of the CC carriers [(86.13 ± 34.77) ng/L vs. (102.50 ± 27.52) ng/L, P < 0.05]; (4) In the restenosis group, the 24 h post-PCI serum level of IL-10 in the A allele carriers was also significantly lower than that in those without the A allele [(78.51 ± 34.09) ng/L vs. (102.19 ± 33.66) ng/L, P < 0.05]; (5) Logistic regression analysis revealed positive correlations between acute coronary syndrome patients, pre-PCI degree of stenosis, length of target stenosis lesion and restenosis (OR = 5.90, 1.86, 2.83 respectively); and there were negative correlations between 24 h post-PCI serum level of IL-10, the stent diameter, the diameter of reference vessel before stent implantation and restenosis(OR = 0.99, 0.70, 0.46 respectively). CONCLUSION: (1) The IL-10 gene -592 C/A polymorphism was not associated with restenosis in the Tianjin Chinese Han population; (2) IL-10 is an early post-PCI inflammatory cytokine, 24 h post-PCI serum IL-10 level was an independent predictive factor for restenosis, the IL-10 A allele carriers may have increased incidence of in-stent restenosis (ISR) by reducing the serum IL-10 levels.
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Angioplastia Coronária com Balão , Povo Asiático/genética , Reestenose Coronária/genética , Interleucina-10/genética , Polimorfismo Genético , Stents , Adulto , Idoso , Feminino , Genótipo , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To examine the expression of angiotensin II (Ang II) receptor subtypes in human left and right atrial tissue in atrial fibrillation underlying rheumatic heart disease. METHODS: Atrial tissue samples were obtained from 39 patients with rheumatic heart disease, 25 with atrial fibrillation (AF) and 14 with sinus rhythm(SR) during open heart surgery. AT1 and AT2 mRNA levels were measured with semi-quantitative reverse transcription polymerase chain reaction techniques. AT1 and AT2 protein levels were measured with immunohistochemical techniques. RESULTS: Compared with that of the SR group, left atrial inner diameter was significantly increased in the patients of the AF group. The AT1 mRNA and protein levels in the LA significantly increased in patients with AF compared with those in patients with SR (P < 0.05), whereas AT2 mRNA and protein were not significantly altered. Investigations of Ang II receptor subtypes' mRNA and protein levels in the RA did not exhibit any significant changes either in AT1 or AT2 in patients with AF and SR. CONCLUSIONS: AF is associated with an up-regulation of AT1 in LA, but does not appear to influence the AT2 expression. This may indicate a possible pathophysiologic role for renin-angiotensin system in the development of AF. The series of effects mediated by AT1 activation may be one of the molecular mechanisms involved in the process of atrial remodeling.
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Fibrilação Atrial/metabolismo , Receptores de Angiotensina/metabolismo , Cardiopatia Reumática/metabolismo , Adulto , Fibrilação Atrial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina , Cardiopatia Reumática/complicaçõesAssuntos
Cilazapril/uso terapêutico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Animais , Anti-Hipertensivos/uso terapêutico , Modelos Animais de Doenças , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Infarto do Miocárdio/tratamento farmacológico , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Valina/uso terapêutico , ValsartanaRESUMO
OBJECTIVE: To construct pGL2-ApoA I luciferase reporter vector containing ApoA I gene regulation area, and to investigate the effect of G --> A and C --> T substitution in ApoA I promoter -75 bp and intron 1 +83 bp region respectively on ApoA I gene expression. METHODS: Human chromosome DNA fragments containing ApoA I gene were amplified by PCR, and the DNA fragments consisting of ApoA I AA/CC, GG/TT and GG/CC genetypes were selected separately, then pUC vector including above three different DNA fragments was constructed. After digesting pUC vector with Sac I and Bgl II, ligate the different DNA fragments to basic pGL2 vector that containing luciferase reporter gene. Recombinant and PRL-null vector were cotransfected into HepG2 cells by using cationic liposome method. Cells were cultured for 48 h, activity of firefly and renills luciferase was measured. RESULTS: Three vectors with pGL2-ApoA I-L(-2500 to +289 bp) long fragment vectors and 3 with pGL2-ApoA I-S(-145 to +289 bp) short fragment vectors were combinated successfully. Relative activity of luciferase for ApoA I AA/CC or GG/TT was lower than that for GG/CC significantly. CONCLUSION: -75 bp G --> A and +83 bp C --> T substitution in ApoA I gene may inhibit ApoA I gene transcription and expression. It may be the reason why subjects containing -75 bp A and +83 bp T have lower high density lipoprotein cholesterol (HDL-C) concentration.
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Apolipoproteína A-I/genética , Íntrons , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Apolipoproteína A-I/metabolismo , Linhagem Celular Tumoral , HDL-Colesterol/metabolismo , Vetores Genéticos , Humanos , Luciferases/genética , Luciferases/metabolismo , Mutação Puntual , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , TransfecçãoRESUMO
OBJECTIVE: To reveal the association of 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor 1 gene (PAI1) with plasma PAI1 level in deep vein thrombosis (DVT) in Chinese Han ethnic group. METHODS: One hundred and twenty Chinese DVT patients and 120 healthy controls were recruited. The PAI1 promoter 4G/5G polymorphism was detected using polymerase chain reaction (PCR). The antigen of tissue-type plasminogen activator (tPA) or PAI1 was quantified by a commercially available enzyme-linked immunosorbent assay (ELISA) in DVT cases and health controlsì respectively. RESULTS: Neither in the distribution of PAI1 promoter 4G/5G polymorphism nor in the frequencies of 4G and 5G allele was there a difference between two groups. The levels of PAI1 antigen in the carriers of the 4G/4G genotype were significantly higher than those either in the 4G/5G genotype or in the 5G/5G genotype; In the 4G/5G genotype or in the 5G/5G genotype the TG levels are an independently determinant factor of PAI1 antigen levels. CONCLUSION: There is a close relationship of the PAI1 4G/5G polymorphism to its plasma level in deep vein thrombosis in Chinese Han ethnic group, although lack of association between this genetic variation and risk of DVT suggest no major cause-effect pathogenic role of this polymorphism by itself.
Assuntos
Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Trombose Venosa/genética , Adulto , Idoso , Estudos de Casos e Controles , Eletroforese , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Trombose Venosa/sangueRESUMO
OBJECTIVE: To investigate serum level and gene polymorphisms of matrix metalloproteinase 9 (MMP-9), and platelet glycoprotein VI (GPVI) in patients with acute coronary syndrome (ACS). METHODS: In a prospective study of 179 patients with documented ACS and 164 controls, we measured baseline serum MMP-9 levels using ELISA and determined the MMP-9/C-1562T and MMP-9/G5564A genotypes using PCR-restriction fragment length polymorphism. Fib serum level was measured by Clauss assay. We also analyzed the Fib/Bbeta-148C/T and GPVI/T13254C polymorphisms. RESULTS: Serum levels of MMP-9 and Fib in ACS patients were significantly higher than in controls (P < 0.001), and serum level of Fib in the acute myocardial infarction group was higher than in patients with unstable angina (P < 0.05). No significant difference between ACS patients and controls was found in frequencies of MMP-9/C-1562T, MMP-9/G5564A, Fib/Bbeta-148C/T, and GPVI/T13254C genotypes and alleles (P > 0.05). The T allele of the Fib/Bbeta-148T polymorphism was associated with increased plasma Fib level (P < 0.05). There was a strong positive correlation between serum level of MMP-9 and Fib (r = 0.289, P < 0.01). CONCLUSION: Serum levels of MMP-9 and Fib were independent risk factors of ACS. There was an obvious relationship between the Bbeta-148C/T mutation and high Fib level. No significant difference between controls and ACS patients was found in the frequencies of MMP-9 C-1562T and G5564A, Fib Bbeta-148C/T and GPVI T13254C genotypes and alleles (P > 0.05).