The Angiotensinogen T235 Variant and the Use of Antihypertensive Drugs in a Population-Based Cohort

Abstract

Variants of the angiotensinogen gene may increase the risk of developing arterial hypertension, but their effect on the use of antihypertensive medication in the general population remains unclear. Thus, we determined T174M and M235T allele status and angiotensinogen plasma levels in a cross-sectional sample of 634 middle-aged subjects (48.4% men) from the Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg cohort study. We found no association between T174M allele status and angiotensinogen levels, blood pressure, or use of antihypertensive drugs. In contrast, multivariate analysis revealed that individuals who carried at least one copy of the T235 allele (n=418) had higher systolic and diastolic pressures ( P =.007 and .008, respectively) and were more likely to use an antihypertensive drug (1.6-fold risk, P =.04) than homozygotes for the M235 allele (n=216). The likelihood of taking two or more antihypertensive medications was 2.1-fold higher in carriers of the T235 allele ( P =.02). Overall, 22.5% of all antihypertensive drugs taken appeared to be attributable to the excess risk associated with this allele. These associations were replicated in two previous surveys carried out on the same individuals over 10 years. Furthermore, the T235 allele was related to higher angiotensinogen plasma levels [15.5±0.31 versus 16.5±0.15 (nmol/L)/L in homozygotes for the M235 and T235 alleles, respectively; P <.01], which were also related to systolic pressure ( P =.03) and more intensive antihypertensive medication ( P =.03). We conclude that the angiotensinogen T235 allele accounts for a substantial proportion of antihypertensive drug use in this middle-aged, population-based group of white subjects.