Effects of ACE I/D and AT1R-A1166C polymorphisms on blood pressure in a healthy normotensive primary care population:: first results of the Hippocates study

Background Several studies have assessed the relationship between the angiotensin-converting enzyme (ACE) I/D or angiotensin 11 type 1 receptor (AT(1)R)-A(1166)C polymorphisms and blood pressure (BP). Since most data have been obtained in selected populations, the present study was performed in a healthy normotensive primary care population. Objective To investigate the individual effects of the aforementioned polymorphisms and their interaction on BP. Methods This cross-sectional study included 198 healthy subjects. Office BP was measured and polymorphisms were genotyped (polymerase chain reaction). Polymorphism interaction was tested using the following model: systolic blood pressure (SBP) (or diastolic blood pressure, DBP) = b(0) + b(1)X + b(2)Y + b(3)XY, in which X and Y represent the polymorphisms' risk alleles. Results The ACE I/D polymorphism was associated with SBP (P = 0.002) and DBP (P = 0.004); highest pressures tracked with the DD genotype. Furthermore, in multiple linear regression analysis the ACE D allele was associated with SBP (P = 0.005) and DBP (P = 0.001), when adjusted for body mass index (BMI) and age. With respect to the AT(1)R-A(1166)C polymorphism, SBP was highest in the CC genotype (P = 0.025). In linear regression analysis the C allele was not associated with SBP. No synergistic effect of ACE D and AT, R C alleles on BP was found. Nevertheless, highest DBP tracked with the DDCC combination in comparison with other homozygous allele combinations (P = 0.030). Conclusions This study confirmed an association of ACE I/D and AT(1)R-A(1166)C polymorphisms with BP in a healthy normotensive primary care population. Although synergistic effect of both polymorphisms on BP does not seem to be present, an additive effect on DBP is likely. (C) 2003 Lippincott Williams Wilkins.