Early Inflammatory and Metabolic Changes in Association With AGTR1 Polymorphisms in Prehypertensive Subjects

Abstract

BACKGROUND The Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in 2003 created a prehypertension category for persons with blood pressures ranging from systolic blood pressure (SBP) of 120–139 mm Hg or diastolic blood pressure (DBP) from 80 to 89 mm Hg, due to increased risk of cardiovascular disease. METHODS Our study utilized the University of California-San Diego (UCSD) Twin Hypertension Cohort. We measured comprehensive plasma cholesterol levels and metabolic (glucose, insulin, leptin) and inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP), free fatty acids) to determine the differences between normotensive and prehypertensive subjects. Additionally, we determined whether angiotensin II receptor type-1 (AGTR1) polymorphisms, previously associated with hypertension, could predict prehypertension. RESULTS A total of 455 white subjects were included in the study (mean age 37.1 years). Prehypertensive subjects were older with greater body mass index (BMI) than the normotensives, and after adjusting for sex and age, had greater plasma glucose, insulin, and IL-6. The common AGTR1 A1166C (rs5186) polymorphism in the 3′-UTR region, particularly the presence of the 1166C allele, which fails to downregulate gene expression, predicted greater likelihood of being in the prehypertension group and higher SBP. A lesser-studied polymorphism in intron-2 of AGTR1 (A/G; rs2276736) was associated with plasma high-density lipoprotein (HDL) and apolipoprotein A-1. In a subgroup analysis of nonobese subjects (N = 405), similar associations were noted. CONCLUSION Prehypertensive subjects already exhibit early pathophysiologic changes putting them at risk of future cardiovascular disease, and AGTR1 may also contribute to this increased risk. Further investigation is needed to confirm these findings and the precise molecular mechanisms of action.

Pretreatment with Antioxidants Augments the Acute Arterial Vasoconstriction Caused by Diesel Exhaust Inhalation

“…In particular, we stratified on the common A1166C polymorphism (rs5186) in the 39-untranslated region of the AGTR1 gene, based on its impact on mRNA stability and subsequent transcription of the AGTR1 receptor. When the CC or AC polymorphism is present, there is an increase in AGTR1 levels, which correlates with elevated blood pressures (44,48). Similarly, we found that subjects with the AC/CC allele exhibited greater vasoconstriction after DE exposure compared with the common AA allele.…”

Autonomic and Hemodynamic Origins of Pre-Hypertension

“…Finally, while we focused on autonomic and hemodynamic determinants of BP in this report, our prehypertensives demonstrated a BMI increment of ~2.9 kg/m 2 over their normotensive counterparts; in other reports, an early elevation of BMI in prehypertension, with its associated metabolic traits, may also be central to the syndrome (41). …”

Genetic variations in MOV10 and CACNB2 are associated with hypertension in a Chinese Han population

“…Angiotensin II receptor type-1 (AGTR1) is a G-protein coupled receptor for angiotensin II, especially in the heart and kidney, and has been studied in many health conditions, including heart failure and stroke (Henskens et al, 2007;Wu et al, 2009). AGTR1 polymorphisms are associated with the susceptibility to hypertension and prehypertension in the American population (Mottl et al, 2008;Fung et al, 2011). A meta-analysis also found that the AGTR1 variant has been associated with an increased risk of hypertension in the Chinese population (Levy et al, 2009).…”