Angiotensin II Type 1 Receptor Gene Polymorphism Predicts Development of Hypertension and Metabolic Syndrome

BACKGROUND: The aim of the study was to investigate the effect of polymorphism A1166C for AGTR1 and -1332G/A for AGTR2 on the incidence of sustained hypertension (HT) and metabolic syndrome in a cohort of young patients screened for stage 1 HT. METHODS: We assessed 420 white hypertensive subjects never treated for HT and followed up for 7.3 years in the HT and Ambulatory Recording Venetia Study (HARVEST). Incident physician-diagnosed HT, increase in ambulatory blood pressure (BP), and new onset metabolic syndrome were the outcome measures. RESULTS: For AGTR1, 37.2% of the subjects in the group with AA genotype, 47.5% in the group with AC genotype, and 66.7% in the group with CC genotype developed HT during follow-up (P = 0.001). Ambulatory systolic (P = 0.007) and diastolic (P < 0.001) BPs increased largely in the patients with CC genotype than in the rest of the group. New onset metabolic syndrome during follow-up (n = 30, P = 0.008), and the frequency of the metabolic syndrome at the end of follow-up (n = 65, P = 0.002) were also more common among the patients with CC and AC genotype. In a Cox analysis, subjects with CC genotype had an increased risk of developing HT (hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.2-2.0, P = 0.000) and metabolic syndrome (HR 2.8, 1.5-5.2, P = 0.002) than AA subjects. No association was found between the AGTR2 polymorphism and any outcome measure. CONCLUSIONS: The AGTR1 A1166C polymorphism may be considered a genetic marker predisposing to an increase in BP and the development of the metabolic syndrome in subjects screened for stage 1 HT.