ObjectiveTo investigate a possible involvement of polymorphisms of the renin-angiotensin system in predisposition to moderate and severe hypertension and their relationship to parental histories of myocardial infarction and stroke.MethodsHypertensive cases (453 men, 326 women) were patients followed up by general practitioners for established hypertension. Inclusion criteria were an age of onset of hypertension < 60 years and a diastolic blood pressure > 105 mmHg without antihypertensive medication or > 100 mmHg under treatment. Normotensive controls were selected from population-based samples (362 men) and during a preventative medicine visit (170 women). Polymorphisms of the angiotensinogen gene (AGT M235T and T174M), the angiotensin I converting enzyme gene (ACE I/D), and the angiotensin II type 1 receptor gene (AGT1R A1166C) were investigated.ResultsThe AGTT235allele prevalence was higher among male hypertensive cases than it was among controls (0.46 versus 0.40,P= 0.01) and a similar trend was observed with female cases whose hypertension had been diagnosed before they were aged 45 years (0.44 versus 0.38,P= 0.20). The AGT1RC1166allele prevalence was higher among female hypertensives than it was among controls (0.30 versus 0.23,P= 0.03) but no such difference was observed for men. The AGT T174M and ACE I/D polymorphisms were not associated with hypertension. Hypertensive patients reporting a parental history of myocardial infarction before age 60 years had a higher prevalence of the ACEDallele than did those without such a parental history (0.68 versus 0.56,P= 0.01). The ACEDallele prevalence was also greater among patients reporting a parental history of stroke incidence before age 65 years (0.66 versus 0.57,P= 0.05).ConclusionsThese results support the hypothesis that the AGT gene plays a role in predisposition to hypertension and that the ACE gene plays a role in predisposition to acute ischemic events.