RESUMO
To date, the human angiotensinogen (AGT) gene and some of its variants represent the best examples of genetic influences that are involved in the determination of essential hypertension (EH) and associated cardiovascular diseases (CVDs). To assess the value of genotyping AGT in a genetically homogeneous population, we carried out a retrospective, case control study of variants M235T and T174M for putative correlations with CVDs among nationals from the United Arab Emirates (Emirati)--an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 229 Emirati (119 males and 110 females), comprising groups of controls and patients with clinical diagnoses of EH, left ventricular hypertrophy (LVH), ischaemic heart disease (IHD) and myocardial infarction (MI). M235T and T174M alleles were determined via assays based on the polymerase chain reaction. T174M showed no correlation with any of the four clinical entities included in this study. T235 alleles, however, occurred more frequently in the EH group and less frequently in the group of MI survivors. We also found that T235 allele frequencies decreased with age, indicating that in the Emirati population, T235 alleles are associated with a reduced life span and that this effect could occur through independent mechanisms underlying genetic susceptibilities to both EH and MI.
Assuntos
Angiotensinogênio/genética , Genes/genética , Hipertensão/genética , Infarto do Miocárdio/genética , Adulto , Idoso , Alelos , Substituição de Aminoácidos , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol/sangue , Análise Mutacional de DNA , Feminino , Testes Genéticos , Genótipo , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Infarto do Miocárdio/epidemiologia , Isquemia Miocárdica/genética , Fenótipo , Projetos Piloto , Estudos Retrospectivos , Estatística como Assunto , Emirados Árabes Unidos/epidemiologia , Disfunção Ventricular Esquerda/genéticaRESUMO
As a key enzyme of the renin-angiotensin-aldosterone system, the renin gene (REN) is a good candidate quantitative trait locus that may be implicated in the molecular etiology of essential hypertension. Among mixed reports on the subject, a REN MboI restriction fragment length polymorphism has been shown to be significantly associated with a family history of hypertension in a Japanese population. We show here that the REN MboI dimorphic site is located in the ninth intron of the gene, and we describe a polymerase chain reaction-based assay for detection of this site. We investigated MboI genotype distributions in 331 hypertensive and 279 normotensive subjects from the United Arab Emirates (UAE), a genetically homogeneous ethnic population with no history of smoking or alcohol consumption. A statistically significant association was found between alleles on which the MboI site is present and clinical diagnosis of essential hypertension, indicating that 1) the presence of the MboI site is a marker for susceptibility to hypertension in the UAE (the associated odds ratio is 3.16); and 2) variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with this marker play a role in the development of essential hypertension in the UAE.
Assuntos
Hipertensão/genética , Renina/genética , DNA Metiltransferases Sítio Específica (Adenina-Específica)/genética , Envelhecimento/fisiologia , Alelos , Índice de Massa Corporal , Colesterol/sangue , DNA/biossíntese , DNA/genética , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Característica Quantitativa Herdável , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Caracteres Sexuais , Emirados Árabes UnidosRESUMO
We have studied an insertion/deletion (I/D) dimorphism located in the second intron of the human atrial natriuretic factor (ANF) gene among 232 United Arab Emirates (UAE) nationals (112 normotensives and 120 hypertensives) from the Abu Dhabi Emirate, with a view to evaluating the value of this marker in relation to hypertension. Our findings show that genotype frequencies of this I/D marker occur in Hardy-Weinberg proportions (respective genotype frequencies in the overall sample population are: II, 51%; ID, 42%; DD, 7%). No association, however, was evidenced between this dimorphic site and clinical diagnosis of essential hypertension. This suggests that: 1) this I/D dimorphism is not a useful marker to study the relationship between the ANF gene and hypertension in the UAE; and 2) variations of the ANF gene that may be in linkage disequilibrium with this marker do not play a major role in the determination of hypertension in this Arab population.
Assuntos
Fator Natriurético Atrial/genética , Hipertensão/genética , Alelos , Árabes , Estudos de Casos e Controles , DNA/análise , DNA/genética , Feminino , Marcadores Genéticos , Genótipo , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Emirados Árabes Unidos/epidemiologiaRESUMO
We have studied an insertion/deletion dimorphism in the human angiotensin-converting enzyme gene amongst UAE nationals from the Abu Dhabi Emirate. Our findings show lack of association between the I/D allele marker system and clinical diagnosis of essential hypertension, suggesting that variations of the angiotensin-converting enzyme gene do not play a major role in the determination of elevated blood pressure in this Arab population. This agrees with results reported on other ethnic groups.
