RESUMO
The effect of polymorphisms of the RAS genes on the incidence of hypertension seems to be population-dependent. We studied the effects of the angiotensinogen T174M and M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of hypertension among Hispanics. We selected all cases (n=256) and 257 age and sex group-matched controls from a random sample of free living Colombians (n=2,989). Logistic regression was used to estimate the independent effect of each polymorphism. All polymorphisms were in Hardy-Weinberg equilibrium in controls, with the exception of M235T, which showed a small excess of heterozygotes (p=0.005; disequilibrium coefficient, D=-0.0264). After adjustment for age, sex, body mass index, race, physical activity, family history of hypertension and cardiovascular disease, and other polymorphisms, subjects with the ACE DD genotype were 1.56 times (95% confidence interval [CI]: 1.05, 2.33) more likely to be hypertensive than carriers of the I allele (p=0.03). Also, adjusted systolic and diastolic blood pressure were 4.58 (95% CI: -0.39, 9.56) and 3.32 (95% CI: 0.78, 5.86) mmHg higher in DD homozygous individuals than in carriers of the I allele, respectively. Approximately 15% of the cases of hypertension in this population could be attributed to carriage of the DD genotype. None of the other polymorphisms was associated with either hypertension or blood pressure level. In conclusion, the ACE DD genotype appears to be an independent risk factor for development of hypertension and may explain a significant fraction of incident cases among Hispanics.
Assuntos
Hipertensão/etnologia , Hipertensão/genética , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Angiotensinogênio/genética , Pressão Sanguínea/genética , Estudos de Casos e Controles , Colômbia , Feminino , Deleção de Genes , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional/genética , Peptidil Dipeptidase A/genética , Receptor Tipo 1 de Angiotensina/genéticaRESUMO
BACKGROUND: The ACE gene insertion/deletion polymorphism has been studied as a risk factor for acute myocardial infarction (AMI) in different populations with conflicting results. MATERIAL/METHODS: We conducted a case-control study in first AMI cases matched by age (+/-5 years) and sex to controls with non-cardiac diseases to ascertain whether Colombian carriers of the DD genotype were at higher risk of AMI than carriers of the ID and II genotypes. Zygosity for the deletion-insertion (D-I) of the ACE gene polymorphism was determined by polymerase chain reaction. Logistic regression with adjustment for matching factors was used to estimate the independent effect of the DD polymorphism after controlling for traditional cardiovascular risk factors. RESULTS: Participants (n=202) had a mean age of 62 years and 32% were women. The distribution of the polymorphism was significantly different (p=0.001) in cases (II 8.9%; ID 51.5%; DD 39.6%) and controls (II 8.9%; ID 64.4%; DD 26.7%). After adjustment for other risk factors, the risk of AMI in subjects with genotype DD was 1.98 times higher than the risk in the combined group of genotypes II and ID (95% CI: 1.01, 3.87; p=0.04). There was a significant DD by age interaction (p=0.002). In subjects p=0.86), while in subjects <60 years the risk increased 5.16 times (95% CI: 1.68, 15.90; p=0.004). CONCLUSIONS: These results support an increased risk of AMI in Colombian subjects <60 years with the ACE DD genotype.