RESUMO
BACKGROUND: Cardiovascular diseases (CVDs) are the major cause of mortality and morbidity worldwide. Myocardial infarction (MI) is a complex multi-factorial, polygenic disorder arising from an interaction between genetic makeup of individuals and various environmental factors. CYP2C8, CYP2C9 and CYP2J2 gene involved in the metabolism of arachidonic acid, generates epoxyeicosatrienoic acids (EETs) that mediate dilation of coronary arteries improving post-ischemic cardiac contractile function, reduce vascular inflammation, and increase intravascular fibrinolysis. The study is aimed at analyzing the association of CYP2C8, CYP2C9 and CYP2J2 gene polymorphisms and MI risk in the South Indian population. METHODS: This retrospective study consisted of 287 MI patients, 279 risk control patients and 321 healthy individuals. Blood samples were collected from all the subjects and DNA was isolated using standard phenol-chloroform method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real time-polymerase chain reaction (RT-PCR) methods were used for genotyping. To test the potential independent association between polymorphisms and the risk of MI, Multiple-logistic regression analysis was performed. RESULTS: Our findings displayed a significant association between CYP2J2*7 (p=0.04; OR=2.0) polymorphism and MI while comparing cases with to risk controls. We did not observe any association of CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3 with MI. CONCLUSION: Our results suggest that individuals with any conventional risk factor for MI along with CYP2J2*7 variant allele may be predisposed to risk of MI in South Indian population.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2C9/genética , Sistema Enzimático do Citocromo P-450/genética , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/genética , Povo Asiático , Citocromo P-450 CYP2J2 , DNA/genética , Feminino , Genótipo , Heterozigoto , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Estudos Retrospectivos , Fatores de RiscoRESUMO
Myocardial infarction (MI) is a complex multi-factorial, polygenic disorder which results from an interaction between a person's genetic makeup and various environmental factors. Nitric oxide (NO), a potent vasodilator produced by endothelial cells, plays an important role in the regulation of blood pressure, regional blood flow and also inhibits platelet aggregation, vascular smooth muscle cell proliferation and leukocyte adhesion to vascular endothelium. Our aim was to analyze the association of NOS3 (endothelial nitric oxide synthase 3) 894G>T and -786T>C gene polymorphisms and MI risk in the South Indian population. A total of 287 MI patients, 279 risk control patients and 321 healthy controls were recruited for the retrospective study. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was no significant association observed between NOS3 894G>T, -786T>C polymorphisms and MI. A significant difference was observed in the distribution of GT genotype of the NOS3 894G>T polymorphism between the cases and the risk controls (p = 0.05) but the odds ratio (0.6) did not show risk for MI. The present study showed lack of association between NOS3 gene polymorphisms and MI in South Indian population.
Assuntos
Infarto do Miocárdio/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genes Dominantes , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Índia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Infarto do Miocárdio/enzimologia , Polimorfismo de Fragmento de Restrição , Risco , Análise de Sequência de DNARESUMO
INTRODUCTION: In association with candidate genes, the observed trait may be due to either one of the variant alleles or the interaction of variant alleles at different loci, which are in linkage disequilibrium. AIM: The objective of this study was to investigate the baseline allele and genotype frequencies, linkage disequilibrium (LD) patterns, and haplotype structures of common variants of the CYP2C8, CYP2C9, and ADRB1 genes located on chromosome 10. METHODS: Two hundred and forty-five healthy subjects were recruited from South India and were compared with the HapMap Project's population for LD pattern, allele and genotype frequencies, and haplotype structures. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism and TaqMan assay on real-time polymerase chain reaction. RESULTS: A significant ethnic difference was found in the LD patterns among the variant alleles between the South Indian population and other major ethnic groups, namely African, European, Chinese, and Japanese. CONCLUSION: This study established the normative allele and genotype frequencies, haplotype structure, and LD patterns of common variants of the CYP2C8, CYP2C9, and ADRB1 genes in a South Indian population (Tamilian). The data may be helpful to plan candidate gene-trait association studies in this population.
