F2-Isoprostane level is associated with the angiotensin II type 1 receptor -153A/G gene polymorphism

• Published in: Free radical biology & medicine 2005-03, Vol.38 (5), p.583-588
• Main Authors: Ormezzano, Olivier, Cracowski, Jean-Luc, Mallion, Jean-Michel, Poirier, Odette, Bessard, Janine, Briançon, Serge, François, Patrice, Baguet, Jean Philippe
• Format: Article
• Language: English
• Subjects: Adult; Angiotensin II - physiology; F2-Isoprostanes - metabolism; Female; Humans; Hypertension - genetics; Male; Middle Aged; Oxidative Stress - physiology; Polymorphism, Genetic; Receptor, Angiotensin, Type 1 - genetics; Renin-Angiotensin System - genetics
• ISSN: 0891-5849
• DOI: 10.1016/j.freeradbiomed.2004.11.028

Recent studies have shown that F2-isoprostane levels-a marker for lipid peroxidation-are increased in human renovascular hypertension but not in essential hypertension. Angiotensin II specifically stimulates F2-isoprostane production through activation of the AT1 receptor. The objective was to determine whether there is a relationship between the level of oxidative stress evaluated by measuring urinary F2-isoprostanes levels and polymorphisms of genes involved in the renine angiotensin aldosterone system (RAAS) regulation. The population studied included 100 subjects, 65 of whom were healthy normotensives; the other 35 were suffering from untreated, essential hypertension. The polymorphisms studied concern the genes encoding angiotensin I-converting enzyme (ACE/in16del/ins), angiotensin II receptor type I (AGTR1/A+39C[A+1166C] and AGTR1/A-153G), angiotensinogen (AGT/M235T), and aldosterone synthase (CYP11B2/T344C). Oxidative stress was evaluated by measuring urinary F2-isoprostanes levels. The characteristics of the population were as follows: men/women = 46/56; age = 50 +/- 10 years; BMI = 24 +/- 3 kg/m2; SBP = 131.7 +/- 17.2 mm Hg; DBP = 84.6 +/- 10.4 mm Hg. In univariate analysis, urinary F2-isoprostane levels were significantly lower in the presence of the G allele of AGTR1/A-153G (56 +/- 17 vs 76 +/- 39 pmol/mmol creatinine; P < 0.001, and P < 0.01 after Bonferroni correction for 10 tests). In multivariate analysis, taking into account BP, age, gender, BMI, plasma glucose, and total cholesterol, the G allele of AGTR1/A-153G is linked independently to urinary F2-isoprostanes level (P < 0.01). Our data suggest that F2-isoprostane level depends at least in part on the A-153G polymorphism of the angiotensin II AT1 receptor gene. The clinical and prognostic relevance of this polymorphism requires further investigation.