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-g polymor phism (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 sib pairs, discordant pairs, sibships, extended pedigrees), target different et hnic groups (Caucasian, African-American, Japanese, Chinese), and have diff erent inclusion/exclusion criteria. However, the protocols and definitions were standardized across networks before data collection to allow maximum p oolability. Methods Each network/racial group was analysed separately, using generalize d linear models that accounted for the non-independence of family members a nd/or the confounding of anti-hypertensive medications as needed. The resul ts were also pooled using a pre-planned metaanalysis technique. Results AGT-6 was not significantly associated with blood pressure in any n etwork/racial group. In the meta-analysis, the pooled effect of AGT-6 was s mall [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 crit eria for Stage I hypertension (blood pressure > 140/90 mmHg or medicated) s howed 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. J Hypertens 2000, 18:867-876 (C) Lippincott Williams & Wilkins.