Interaction between the C(−344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study

Objective To study the interaction between the C(-344)T CYP11B2 polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. Design Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. Setting Medical centre of the Olivetti factories. Participants In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. Main outcome measures Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. Results In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic (P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P < 0.001 and TC, P = 0.005), but not in CC homozygotes (P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 ± 0.6, versus CC: - 0.4 ± 1.5 mmHg, P= 0.04). Conclusion Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of CYP11B2 C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.