GENETIC-VARIATION AT THE ANGIOTENSINOGEN LOCUS IN RELATION TO HIGH BLOOD-PRESSURE AND MYOCARDIAL-INFARCTION - THE ECTIM STUDY

Objectives: To study the association between polymorphisms of the angi otensinogen (AGT) gene and blood pressure in population-based samples, and to determine whether genetic variation at the AGT locus is involv ed in the susceptibility to myocardial infarction. Methods: The study population comprised 630 cases who survived a myocardial infarction, r ecruited from the World Health Organization Monitoring Cardiovascular Diseases registers in Belfast, Lille, Strasbourg and Toulouse, and 741 controls drawn from the corresponding populations. The AGT polymorphi sms investigated were T174M and M235T. High blood pressure was defined as diastolic blood pressure >100 mmHg or the use of antihypertensive medication, or both. Results: In the controls the mean+/-SEM frequency of the M174 allele was 0.116+/-0.008, and that of the T235 allele was 0.401+/-0.013. In the whole population blood pressure levels and prev alence of high blood pressure did not vary according to T174M and M235 T genotypes. However, obesity appeared as a crucial factor influencing the relationship between high blood pressure and T174M. In subjects w ith body mass index <26 kg/m(2) there was a 2.4-fold increase of the p revalence of high blood pressure in carriers of the M174 allele compar ed with in homozygotes for the T174 allele, whereas no association was detected in subjects with body mass index >26 kg/m(2). The associatio n between high blood pressure and M235T was not significant in either group. The T174M and M235T genotype distributions did not differ betwe en survivors of myocardial infarction and controls. Conclusions: These data suggest that the AGT gene could be involved in the predispositio n to high blood pressure in non-overweight, but not in overweight men, possibly reflecting genetically different types of hypertension. No s ignificant impact of the ACT locus in the risk of non-fatal myocardial infarction was detected.