Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2

Significant correlation of body sodium and potassium with blood pressure (B P) may suggest a role for aldosterone in essential hypertension. In patient s with this disease, the ratio of plasma renin to plasma aldosterone may be lower than in control subjects and plasma aldosterone levels may be more s ensitive to angiotensin II (Ang II) infusion. Because essential hypertensio n is partly genetic, it is possible that altered control of aldosterone syn thase gene expression or translation may be responsible. We compared the fr equency of 2 linked polymorphisms, one in the steroidogenic factor-1 (SF-1) binding site and the other an intronic conversion (IC), in groups of hyper tensive and normotensive subjects. In a larger population, the relationship of aldosterone excretion rate to these polymorphisms was also evaluated. I n 138 hypertensive subjects, there was a highly significant excess of TT ho mozygosity (SF-1) over CC homozygosity compared with a group of individuall y matched normotensive control subjects. The T allele was significantly mor e frequent than the C allele in the hypertensive group compared with the co ntrol group. Similarly, there was a highly significant relative excess of t he conversion allele over the "wild-type" allele and of conversion homozygo sity over wild-type homozygosity in the hypertensive group compared with th e control group. In 486 subjects sampled from the North Glasgow Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population, S F-1 and IC genotypes were compared with tetrahydroaldosterone excretion rat e. Subjects with the SF-1 genotypes TT or TC had significantly higher excre tion rates than those with the CC genotype. The T allele was associated wit h higher excretion rates than the C allele. However, no significant differe nces were found in excretion rate between subjects of different IC genotype . Urinary aldosterone excretion rate may be a useful intermediate phenotype linking these genotypes to raised BP. However, no causal relationship has yet been established, and it is possible that the polymorphisms may be in l inkage with other causative mutations.