RESUMO
In the present study, we evaluated the association of the BAT1, NFKBIL, LTA, and CASP1 single nucleotide polymorphisms and the gene−gene interactions with risk of developing restenosis after coronary stenting. The allele and genotype determination of the polymorphisms (BAT1 rs2239527 C/G, NFKBIL1 rs2071592 T/A, LTA rs1800683 G/A, CASP1 rs501192 A/G, and CASP1 rs580253 A/G) were performed by 5'exonuclease TaqMan assays in 219 patients: 66 patients with restenosis and 153 without restenosis. The distribution of rs2239527 C/G, rs2071592 T/A, and rs1800683 G/A polymorphisms was similar in patients with and without restenosis. Nonetheless, under recessive (OR = 2.73, pCRes = 0.031) and additive models (OR = 1.65, pCAdd = 0.039), the AA genotype of the rs501192 A/G polymorphism increased the restenosis risk. Under co-dominant, dominant, recessive, and additive models, the AA genotype of the rs580253 A/G was associated with a high restenosis risk (OR = 5.38, pCCo-Dom = 0.003; OR = 2.12, pCDom = 0.031; OR = 4.32, pCRes = 0.001; and OR = 2.16, 95%CI: 1.33−3.52, pCAdd = 0.001, respectively). In addition, we identified an interaction associated with restenosis susceptibility: BAT1-NFKBIL1-LTA-CASP1 (OR = 9.92, p < 0.001). In summary, our findings demonstrate that the rs501192 A/G and rs580253 A/G polymorphisms, as well as the gene−gene interactions between BAT1-NFKBIL1-LTA-CASP1, are associated with an increased restenosis risk after coronary stenting.
Assuntos
Caspase 1 , Reestenose Coronária , Predisposição Genética para Doença , Alelos , Caspase 1/genética , Reestenose Coronária/genética , Epistasia Genética , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: The aim of the study was to evaluate the association of miRNA-146a G/C (rs2910164), and miRNA-196a2 C/T (rs11614913) polymorphisms with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. MATERIALS AND METHODS: The polymorphisms were determined in 218 patients with CAD who underwent coronary artery stenting (66 with restenosis and 152 without restenosis) and 611 healthy controls using 5' exonuclease TaqMan assays. RESULTS: The distribution of both polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant and additive genetic models, the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism was associated with increased risk of CAD (OR = 2.18, Pco-dom = 0.006, OR = 1.86, Pdom = 0.002, and OR = 1.52, Padd = 0.002, respectively). All models were adjusted for age, type 2 diabetes mellitus, dyslipidemia, hypertension and smoking habit. The "GT" haplotype was associated with increased risk of developing CAD (OR = 1.36, P = 0.046). CONCLUSIONS: Our data suggests that the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism is associated with the risk of developing CAD, but no association with restenosis was observed.
Assuntos
Doença da Artéria Coronariana/genética , Reestenose Coronária/genética , MicroRNAs/genética , Stents , Idoso , Doença da Artéria Coronariana/terapia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The aim of this study was to establish the association of two polymorphisms of the ß-defensin 1 gene (DEFB1, OMIM#602056) with the risk of developing type 2 diabetes mellitus (T2DM) in a group of Mexican patients. METHODS: The 5'UTR -20 G/A, and -44 C/G polymorphisms of DEFB1 gene were genotyped by 5' exonuclease TaqMan assays in a group of 252 patients with T2DM and 522 healthy control. RESULTS: Under dominant and additive models adjusted for the risk factors, the C allele of the -44 C/G polymorphism was associated with increased risk of T2DM (OR = 1.63, 95% CI = 1.07-2.48, pCdom = 0.021 and OR = 1.42, 95% CI = 1.05-1.91, pCadd = 0.023, respectively). In addition, the linkage disequilibrium analysis showed that AC haplotype was associated with an increased risk of developing T2DM (OR = 4.39, p = 0.04). The in-silico analysis showed that the -44 C allele produces a binding site for the transcription factor Ikaros (IK). CONCLUSION: This study demonstrates that the C allele of -44 C/G polymorphism, as well as haplotype AC are associated with the presence of T2DM in the Mexican population. The variation in this polymorphism of the DEFB1 gene could increase the migration of the macrophages to pancreatic islets accelerate the ß-cell dysfunction in T2DM.
Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , beta-Defensinas/genética , Idoso , Sítios de Ligação , Feminino , Haplótipos , Humanos , Fator de Transcrição Ikaros/metabolismo , Masculino , Pessoa de Meia-Idade , Ligação Proteica , beta-Defensinas/química , beta-Defensinas/metabolismoRESUMO
We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p-value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.
Assuntos
Síndrome Coronariana Aguda/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Lipoproteínas HDL/genética , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Antiphospholipid antibody syndrome is a heterogeneous clinical and biochemical entity. We present the case of a young male with history of venous thromboembolism. This time he presents because of chest ischemic pain associated with ST segment elevation. He was taken to the cath lab to perform a primary percutaneous coronary intervention and a total occlusion of the left anterior descending artery was noted. Successful thrombus aspiration was performed. No stent was deployed. He was taken to the cath lab for a second look angiography and no atherosclerotic lesions were observed, which was confirmed by intravascular ultrasound.
El síndrome de anticuerpos antifosfolípidos es una situación clínica y bioquímica heterogénea. Presentamos el caso de un varón joven con antecedente de tromboembolia venosa que se presentó en esta ocasión por dolor precordial, con elevación del ST en el electrocardiograma. Fue llevado a sala de angiografía para realizar angioplastia primaria y se observó una oclu- sión total ostial de la descendente anterior. Se realizó aspiración manual del trombo. No se realizó angioplastia con balón ni stent. En la angiografía de control a las 48 horas se observó ausencia de trombo y de placas aterosclerosas, lo cual se co- rroboró mediante ultrasonido intracoronario.
Assuntos
Síndrome Antifosfolipídica/complicações , Trombose Coronária/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Adulto , Dor no Peito/etiologia , Trombose Coronária/complicações , Trombose Coronária/terapia , Humanos , Masculino , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapiaRESUMO
The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P Res = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P Res = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22-0.92, P Co-dom = 0.006; OR = 0.61, 95%CI 0.44-0.84, P Dom = 0.002; OR = 0.67, 95%CI 0.48-0.94, P Over-dom = 0.02; and OR = 0.65, 95%CI 0.50-0.94, P Add = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.
Assuntos
Regiões 3' não Traduzidas/genética , Síndrome Coronariana Aguda/genética , Caspase 1/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Síndrome Coronariana Aguda/imunologia , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
Hypertension is a major public health problem affecting about 30% of the adult population and is associated with an increased risk of developing metabolic and cardiovascular disease. Recent reports have shown that the T-cadherin receptor characteristically expressed on endothelial and vascular smooth muscle cells is involved in hypertension. The aim of the present study was to evaluate the role of cadherin-13 (CDH13) gene polymorphisms as susceptibility markers for hypertension in Mexican population. Six CDH13 polymorphisms (rs11646213, rs11646411, rs6563943, rs3096277, rs3784990 and rs254340) were genotyped by 5' exonuclease TaqMan assays in a group of 644 hypertensive and 765 non-hypertensive individuals. Under co-dominant, recessive, and additive models, the CDH13 T>A (rs11646213) polymorphism was associated with decreased risk of developing hypertension when compared to non-hypertensive individuals (OR=0.61, 95% CI: 0.42-0.89, Pco-dom=0.019; OR=0.63, 95% CI: 0.46-0.87, Pres=0.005; OR=0.80, 95% CI: 0.66-0.96, Padd=0.016, respectively). All models were adjusted by gender, age, body index mass, type II diabetes mellitus, alcohol consumption, dyslipidemia and smoking habit. Linkage disequilibrium analysis showed one haplotype (TCACGG) with decreased frequency in hypertensive when compared to non-hypertensive individuals (OR=0.52, 95% CI: 0.33-0.82, P=0.0053). In summary, our data suggests that the CDH13 T>A (rs11646213) polymorphism is associated with decreased risk of developing hypertension in the Mexican population. In addition, it was possible to distinguish one haplotype associated with decreased risk and two for increased risk of develop hypertension.
Assuntos
Caderinas/genética , Genótipo , Hipertensão/genética , Idoso , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 µg/L versus 20.81 µg/L, p = 0.002) and homocysteine (11.36 µmol/L versus 8.81 µmol/L, p < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 µg/L in the patients with bivascular obstruction and 42.77 ± 31.81 µg/L in trivascular coronary obstruction, p = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients.
RESUMO
BACKGROUND: Clopidogrel is a pro-drug and its intestinal absorption is limited by the P-glycoprotein encoded by the ABCB1 gene. It is metabolized hepatically by cytochrome P450 enzymes encoded by CYP genes to produce an active metabolite that antagonizes the P2Y12 platelet receptor. Some patients exhibit poor clopidogrel responsiveness due to polymorphisms, resulting in thrombotic events. The aim of this study was to determine the relationship between poor clopidogrel responsiveness and the ABCB1, CYP and P2RY12 gene polymorphisms among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Two hundred seventy-six patients who underwent PCI were included in this study. Clopidogrel responsiveness was determined via optical aggregometry in platelet-rich plasma using 10 µM ADP. Patients exhibiting a platelet aggregation response higher than 70% were classified as poor responders. The genetic polymorphisms were analyzed via real-time PCR. Poor responsiveness to clopidogrel was noted in 22.1% of the patients. The TT genotype of the C3435T polymorphism of the ABCB1 gene and omeprazole usage were each associated with poor clopidogrel responsiveness (Exp (ß) 2.73, p=0.009 and Exp (ß) 3.86, p=0.04, respectively). CONCLUSION: Poor clopidogrel responsiveness is associated with the TT genotype of the C3435T polymorphism of the ABCB1 gene.
Assuntos
Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Clopidogrel , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo Genético , Ticlopidina/uso terapêuticoRESUMO
The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5' exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Assuntos
Doença da Artéria Coronariana/genética , Polimorfismo de Nucleotídeo Único , Renina/genética , Idoso , Alelos , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Estudos de Casos e Controles , Biologia Computacional , Reestenose Coronária/genética , Feminino , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Técnicas de Genotipagem , Haplótipos , Heterozigoto , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Renina/metabolismo , Fatores de Risco , StentsRESUMO
The aim of the present study was to establish the role of IL-6 and TGF-ß1 gene polymorphisms in the risk of developing in-stent restenosis. Two IL-6 [rs1800796 (-572 G>C), rs2069827 (-1426 T>G)] and two TGF-ß1 [rs1800469 (-509 T>C), rs1800470 (T29C)] gene polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 244 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. Under the dominant and additive models adjusted for hypertension, stable angina, stent used, and diameter of stent, the TGF-ß1 T29C (rs1800470) polymorphism was significantly associated with an increase risk of restenosis when compared to patients without restenosis (OR=2.06, 95% CI: 1.03-4.11, P(Dom)=0.034 and OR=1.64, 95% CI: 1.09-2.45, PAdd=0.016). TGF-ß1 polymorphisms were in linkage disequilibrium and one haplotype (TT) was significantly increased in patients with restenosis when compared to patients without restenosis (OR=2.03, P=0.041). In summary, our results suggest that the TGF-ß1 T29C gene polymorphism could be involved in the risk of developing restenosis after coronary stent placement.
Assuntos
Biomarcadores/metabolismo , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/genética , Interleucina-6/genética , Polimorfismo Genético/genética , Complicações Pós-Operatórias , Stents , Fator de Crescimento Transformador beta1/genética , Idoso , Angiografia Coronária , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , PrognósticoRESUMO
The aim of the present study was to establish the gene frequency of six polymorphisms of the ABCB1, CYP3A5, CYP2C19, and P2RY12 genes in a population resident of Mexico City. The proteins encoded by these genes have been associated with the absorption, and biotransformation of clopidogrel. The ABCB1 T3435C, CYP3A5 V3 A6986G, P2RY12 G52T, P2RY12 C34T, CYP2C19 V2 and V3 (positions G681A and G636A, respectively), polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 269 healthy unrelated Mexican Mestizo individuals. The CYP2C19 V3 G636A polymorphism was not detected in the Mexican Mestizos population. However, the studied population presented significant differences (P < 0.05) in the distribution of the T3435C, A6986G, G681A, G52T and C34T polymorphisms when compared to reported frequencies of Amerindian of South America, Caucasian, Asian, and African populations. In summary, the distribution of the ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms distinguishes to the Mexican Mestizos population from other ethnic groups.
Assuntos
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Etnicidade/genética , Receptores Purinérgicos P2Y12/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , México , Polimorfismo GenéticoRESUMO
Recent studies provide evidence on the emerging role of the SOCS1 gene in the development and progression of atherosclerotic lesions. This gene encodes for the suppressor of the cytokine signaling-1 protein that interacts directly with the Janus kinases that are essential intracellular mediators of the immune cytokine action. The aim of this study was to test for associations between SOCS1 gene single nucleotide polymorphisms (SNPs) and the risk of developing acute coronary syndromes (ACS) in a group of Mexicans patients. Four SNPs [-3969 C>T (rs243327), -1656 G>A (rs243330), -820 G>T (rs33977706) and +1125 G>C (rs33932899)] of SOCS1 gene were determined for TaqMan genotyping assays in a group of 447 patients with ACS and 622 healthy controls. Under heterozygous model, the -3969 C>T (rs243327) SNP was associated with increased risk of ACS (OR=1.45, P(Het)=0.021). On the other hand, under co-dominant and heterozygous models, the -1656 G/A (rs243330) SNP was associated with increased risk of ACS (OR=1.47, P(Co-dom)=0.038 and OR=1.50, P(Het)=0.013, respectively). Moreover, under co-dominant, dominant, and heterozygous models, the -820T/G (rs33977706) SNP was associated with increased risk of ACS (OR=1.59, P(Co-dom)=0.03, OR=1.48, P(Dom)=0.028 and OR=1.61, P(Het)=0.01). Finally, under co-dominant and heterozygous models, the +1125 G/C (rs33932899) SNP was associated with increased risk of ACS (OR=1.54, P(Co-dom)=0.006, OR=1.58, P(Het)=0.012, respectively). Models were adjusted for gender, age, body index mass, dyslipidemia, alcohol consumption, and smoking. In summary, our data suggests that the four studied polymorphisms of the SOCS1 gene play an important role as susceptibility markers for developing ACS.
Assuntos
Síndrome Coronariana Aguda/genética , Polimorfismo de Nucleotídeo Único , Proteínas Supressoras da Sinalização de Citocina/genética , Síndrome Coronariana Aguda/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Proteína 1 Supressora da Sinalização de CitocinaRESUMO
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR=1.31, 95% CI: 1.04-1.66, P=0.018) and decreased frequencies of GAGATG (OR=0.47, 95% CI: 0.25-0.88, P=0.011) and AGAGCA (OR=0.15, 95% CI: 0.02-0.65, P=0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Assuntos
Doença da Artéria Coronariana/genética , Reestenose Coronária/genética , Haplótipos , Peptidil Dipeptidase A/genética , Idoso , Reestenose Coronária/etiologia , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , StentsRESUMO
AIM: To investigate the impact of primary reperfusion therapy (RT) on early and late mortality in acute right ventricular infarction (RVI). METHODS: RVI patients (n = 679) were prospectively classified as without right ventricular failure (RVF) (class A, n = 425, 64%), with RVF (class B, n = 158, 24%) or with cardiogenic shock (CS) (class C, n = 96, 12%). Of the 679 patients, 148 (21.7%) were considered to be eligible for thrombolytic therapy (TT) and 351 (51.6%) for primary percutaneous coronary intervention (PPCI). TIMI 3-flow by TT was achieved for A, B and C RVI class in 65%, 64% and 0%, respectively and with PPCI in 93%, 91% and 87%, respectively. RESULTS: For class A without RT, the mortality rate was 7.9%, with TT was reduced to 4.4% (P < 0.01) and with PPCI to 3.2% (P < 0.01). Considering TT vs PPCI, PPCI was superior (P < 0.05). For class B without RT the mortality was 27%, decreased to 13% with TT (P < 0.01) and to 8.3% with PPCI (P < 0.01). In a TT and PPCI comparison, PPCI was superior (P < 0.01). For class C without RT the in-hospital mortality was 80%, with TT was 100% and with PPCI, the rate decreased to 44% (P < 0.01). At 8 years, the mortality rate without RT for class A was 32%, for class B was 48% and for class C was 85%. When PPCI was successful, the long-term mortality was lower than previously reported for the 3 RVI classes (A: 21%, B: 38%, C: 70%; P < 0.001). CONCLUSION: PPCI is superior to TT and reduces short/long-term mortality for all RVI categories. RVI CS patients should be encouraged to undergo PPCI at a specialized center.
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Endothelial dysfunction plays an essential role in the development and progression of atherosclerotic lesions. Endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) are considered important molecules in the endothelial dysfunction process. The aim of the present study was to evaluate the role of eNOS and ET-1 (EDN1) gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS). Six polymorphisms (rs1799983, rs2070744, rs1800783, rs3087459, rs1800541, and rs5369) of eNOS and EDN1 genes were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 452 patients with ACS and 283 healthy controls. The results showed increased frequencies of the A allele of the END1-914 C>A (rs3087459) polymorphism in ACS patients when compared to controls (OR=1.56, Pc=0.01). Under an additive model, the "AA" genotype was associated with an increased risk of developing ACS, adjusted for gender, hypertension, dyslipidemia, alcohol consumption, smoking, and diabetes (OR=1.56, p=0.045). Linkage disequilibrium analysis showed one EDN1 haplotype (AT) with increased frequency in ACS patients when compared to healthy controls (OR=1.65, Pc=0.0015). The "AT" haplotype was associated with the risk of developing ACS after adjusting for cardiovascular risk factors using multiple logistic analysis. In this case, the adjusted OR was 1.73 for the AT haplotype (Pc=0.0018). In summary, resulting data suggest that the END1-914 C>A gene polymorphism could be involved in the risk of developing ACS in Mexican individuals.
Assuntos
Síndrome Coronariana Aguda/genética , Endotelina-1/genética , Polimorfismo de Nucleotídeo Único , Síndrome Coronariana Aguda/metabolismo , Idoso , Estudos de Casos e Controles , Dislipidemias/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/genéticaRESUMO
BACKGROUND: Inflammation plays an essential role in the development and progression of atherosclerotic lesions. The major histocompatibility complex class II trans-activator (MHC2TA) is considered an important molecule in the inflammatory process regulation. The aim of the present study was to evaluate the role of MHC2TA gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS). METHODS: Three polymorphisms (-168 A>G, 1614 C>G, and 2536 G>A) of the MHC2TA gene were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 297 patients with ACS and 283 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. RESULTS: The 1614 C allele and CC genotype were associated with risk of developing ACS (PC=0.014, OR=1.37 and PC=0.006, OR=1.90, respectively). Based on Hosmer-Lemeshow Goodness of Fit test, the recessive model was selected to estimate risk between ACS patients and controls adjusted by cardiovascular risk factors using a multiple logistic analysis. In this case, the OR adjusted was 1.78 for the 1614 CC genotype (P=0.023). The analysis of linkage disequilibrium showed one risk haplotype (ACG) and one protective haplotype (AGG) for developing ACS (P=0.02, OR=1.5 and P=0.04, OR=0.72, respectively). CONCLUSION: The results suggest that MHC2TA 1614 gene polymorphism could be involved in the risk of developing ACS.
Assuntos
Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/imunologia , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Transativadores/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genes MHC da Classe II/imunologia , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: The aim of this study was to test for association between MHC2TA gene polymorphisms and risk for restenosis after coronary stent placement in a group of Mexican patients. METHODS: The MHC2TA-168A>G (rs3087456), 1614C>G (rs4774), and 2536G>A (rs2229320) single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays in a group of 202 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. RESULTS: The results obtained in this study showed that the frequency of the three polymorphisms studied was similar in patients with and without restenosis. Univariate analysis showed that the use of drug-eluting stent (DES) reduces the risk of developing restenosis (p<0.001, OR=0.26). In contrast, the diameter<2.5mm of the stent and bifurcations increased the risk of developing restenosis (p=0.049, OR=1.74 and p=0.041, OR=1.8). CONCLUSION: The present study suggests that the MHC2TA polymorphisms are not involved in the risk of developing restenosis after coronary stent placement.
Assuntos
Reestenose Coronária/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Stents , Transativadores/genética , Feminino , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Ischemic heart disease is the leading cause of death and heart failure worldwide. That is why it is important to develop new therapeutic modalities to decrease mortality and long-term complications in these patients. One of the main lines of research worldwide is myocardial regeneration, using progenitor cells in order to improve systolic and diastolic function in patients with ischemic heart disease, as well as to increase their survival. There have been carried out, with great enthusiasm worldwide, human and animal studies to define the usefulness of stem cells in the management of patients with ischemic heart disease. Today, regenerative therapy in ischemic heart disease is considered a novel therapeutic tool, with substantial theoretical benefits and few side effects. Here we present the scientific principles that support the use of this therapy, discuss the current clinical evidence available; and point out the controversial issues still not clarified on its use and usefulness in the short and long term.
Assuntos
Isquemia Miocárdica/cirurgia , Transplante de Células-Tronco , Ensaios Clínicos como Assunto , HumanosRESUMO
Objective: The aim of this study was to test for association between MHC2TA gene polymorphisms and risk for restenosis after coronary stent placement in a group of Mexican patients. Methods: The MHC2TA-168A>G (rs3087456), 1614C>G (rs4774), and 2536G>A (rs2229320) single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays in a group of 202 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. Results: The results obtained in this study showed that the frequency of the three polymorphisms studied was similar in patients with and without restenosis. Univariate analysis showed that the use of drug-eluting stent (DES) reduces the risk of developing restenosis (p < 0.001, OR = 0.26). In contrast, the diameter< 2.5 mm of the stent and bifurcations increased the risk of developing restenosis (p = 0.049, OR = 1.74 and p = 0.041, OR = 1.8). Conclusion: The present study suggests that the MHC2TA polymorphisms are not involved in the risk of developing restenosis after coronary stent placement.
Objetivo: El propósito de este estudio fue evaluar la asociación de los polimorfismos del gen MHC2TA y el riesgo de desarrollar reestenosis, después del implante de stent coronario en un grupo de pacientes mexicanos. Métodos: Los polimorfismos de un solo nucleótido MHC2TA-168A>G (rs3087456), 1614C>G (rs4774) y 2536G>A (rs2229320), se determinaron en un grupo de 202 pacientes tratados con stent coronario. Los polimorfismos fueron evaluados utilizando ensayos de genotipificacion Taq-Man 5' exonucleasa. El procedimiento basal y la búsqueda de predictores de reestenosis fueron analizados por medio de angiografía coronaria, y seguimiento angiográfico con el fin de detectar reestenosis binaria. Resultados: Los resultados obtenidos en este estudio mostraron que la distribución génica de los tres polimorfismos estudiados fue muy similar, en pacientes con o sin reestenosis. Sin embargo, el análisis univariado mostró que el uso de los stent medicados reducen el riesgo de desarrollar reestenosis (p < 0.001, OR = 0.26). En contraste, con las bifurcaciones y el diámetro < 2.5 mm del stent que se incrementa el riesgo de desarrollar reestenosis (p = 0.049, OR = 1.74 y p = 0.041, OR = 1.8). Conclusión: El presente estudio sugiere que los polimorfismos del gen MHC2TA no están asociados con el riesgo de desarrollar reestenosis, después del implante de stent coronario.