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

Abstract

Objective: To study the interaction between the C(-344)T 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 C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.