GENE POLYMORPHISMS OF THE RENIN-ANGIOTENSIN SYSTEM IN RELATION TO HYPERTENSION AND PARENTAL HISTORY OF MYOCARDIAL-INFARCTION AND STROKE - THE PEGASE STUDY

Objective To investigate a possible involvement of polymorphisms of th e renin-angiotensin system in predisposition to moderate and severe hy pertension and their relationship to parental histories of myocardial infarction and stroke. Methods Hypertensive cases (453 men, 326 women) were patients followed up by general practitioners for established hy pertension. Inclusion criteria were an age of onset of hypertension le ss than or equal to 60 years and a diastolic blood pressure greater th an or equal to 105 mmHg without antihypertensive medication or greater than or equal to 100 mmHg under treatment. Normotensive controls were selected from population-based samples (362 men) and during a prevent ative 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 (AGT(1)R A1166C ) were investigated. Results The AGTT235 allele 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 who se hypertension had been diagnosed before they were aged 45 years (0.4 4 versus 0.38, P = 0.20). The AGT(1)R C1166 allele prevalence was high er 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 T 174M and ACE I/D polymorphisms were not associated with hypertension. Hypertensive patients reporting a parental history of myocardial infar ction before age 60 years had a higher prevalence of the ACE D allele than did those without such a parental history (0.68 versus 0.56, P = 0.01). The ACE D allele prevalence was also greater among patients rep orting a parental history of stroke incidence before age 65 years (0.6 6 versus 0.57, P = 0.05). Conclusions These results support the hypoth esis 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. (C) 1998 Rapid Science Publishers Ltd.