Lack of association of the angiotensinogen-6 polymorphism with blood pressure levels in the comprehensive NHLBI Family Blood Pressure Program

Objective: To evaluate the association between the angiotensinogen-6 polymorphism (AGT-6) and blood pressure levels. Design: Data were analysed from the first 4322 subjects of the NHLBI Family Blood Pressure Program (FBPP), consisting of four networks (GenNet, GENOA, HyperGEN and SAPPHIRe), each conducting a multicentre observational family study to identify and characterize the genetic determinants of hypertension and blood pressure. The four studies use different designs (concordent sibpairs, discordant pairs, sibships, extended pedigrees), target different ethnic groups (Caucasian, African-American, Japanese, Chinese), and have different inclusion/exclusion criteria. However, the protocols and definitions were standardized across networks before data collection to allow maximum poolability. Methods: Each network/racial group was analysed separately, using generalized linear models that accounted for the non-independence of family members and/or the confounding of anti-hypertensive medications as needed. The results were also pooled using a pre-planned metaanalysis technique. Results: AGT-6 was not significantly associated with blood pressure in any network/racial group. In the meta-analysis, the pooled effect of AGT-6 was small [hazard ratio = 1.10, 95% confidence interval (CI) = 0.99-1.22, P = 0.0647 for systolic; hazard ratio = 1.04, 95% CI = 0.89-1.21, P= 0.6383 for diastolic]. A post-hoc analysis restricting to subjects meeting JNC VI criteria for Stage I hypertension (blood pressure > 140/90 mmHg or medicated) showed a stronger statistically significant relationship for systolic blood pressure (hazard ratio = 1.44, 95% CI =1.04-2.00, P = 0.0283). Conclusions: AGT-6 has minimal to no effect on the interindividual variation of blood pressure levels, and is at best a 'minor gene' for blood pressure in the population as a whole. (C) Lippincott Williams and Wilkins.