RESUMO
AIM: To assess the association of CYP2C19 G681A, P2RY12 H1/H2, and ITGB3 T1565C polymorphisms with the extent of platelet aggregation in patients with coronary heart disease (CHD) during antiplatelet therapy. SUBJECTS AND METHODS: 166 male patients with CHD, living in the Western Siberian Region, were examined. All the patients underwent a test for platelet aggregation induced by ADP (2.5 and 5.0 µm) and epinephrine (0.2 µm). Genotyping was performed using an allele-specific polymerase chain reaction technique. RESULTS: The polymorphic variants of the P2RY12 and ITGB3 genes were ascertained to have no impact on the extent of platelet aggregation in patients receiving clopidogrel and acetylsalicylic acid. An association was found between CYP2C19 681A allele carriage and the increased extent of platelet aggregation induced by ADP. CONCLUSION: The carriage of the cytochrome P450 CYP2C19 681A allele rather than platelet receptor gene polymorphisms determines a risk for clopidogrel resistance in patients with CHD.
Assuntos
Aspirina , Doença da Artéria Coronariana , Citocromo P-450 CYP2C19/genética , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Alelos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Plaquetas/efeitos dos fármacos , Clopidogrel , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Resistência a Medicamentos/genética , Humanos , Integrina beta3/genética , Masculino , Pessoa de Meia-Idade , Farmacogenética , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária/métodos , Polimorfismo Genético , Receptores Purinérgicos P2/genética , Sibéria/epidemiologia , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversosRESUMO
AIM: to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. MATERIALS AND METHODS: Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". RESULTS: Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. CONCLUSION: Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.
Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Isquemia Miocárdica/complicações , Isquemia Miocárdica/genética , Óxido Nítrico Sintase Tipo III/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Idoso , Alelos , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
We studied the association between clopidogrel resistance, H1/NH2 polymorphism of the P2RY12 gene and T156C polymorphism of the GpIIIa gene in residents of Western Siberia suffering chronic CHD. It was shown that the occurrence of H1 and H2 haplotypes of the P2RY12 gene and 1565T and 1565C alleles of the GpIIIa gene was similar to that reported for European populations. Patients showing variable platelet response to the inhibitory action of clopidogrel were not significantly different in terms of P2RY12 and GpIIIa genotype distribution. To conclude, the study revealed no association between the risk of clopidogrel resistance and the presence of polymorphic variants of platelet receptor genes P2RY12 and GpIIIa.
Assuntos
Doença das Coronárias/genética , DNA/genética , Resistência a Medicamentos/genética , Integrina beta3/genética , Polimorfismo Genético , Receptores Purinérgicos P2Y12/genética , Ticlopidina/análogos & derivados , Alelos , Doença Crônica , Clopidogrel , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/metabolismo , Feminino , Genótipo , Humanos , Integrina beta3/metabolismo , Masculino , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Receptores Purinérgicos P2Y12/metabolismo , Ticlopidina/uso terapêuticoRESUMO
We undertook a comparative analysis of allele frequency distribution and I/D polymorphism of the angiotensin converting enzyme (ACE) gene in patients with coronary heart disease (CHD) undergoing coronary stenting with and without signs of restenosis. There were no significant difference between the groups in the genotype frequency distribution of I/D polymorphism of the CAE gene (p = 0.061). The occurrence of D allele in the patients with restenosis was higher than that of I allele (chi-square test 4.117, p = 0.042). Relative risk for the carriers of D and I alleles was 0.35 and 2.83 respectively. It is concluded that the presence of D allele of I/D polymorphism of the CAE gene in patients with chronic CHD may be a risk factor of restenosis of stented coronary arteries.
