Related Experiment Video

Updated: Jul 3, 2026

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model
10:18

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Published on: June 29, 2014

Relation between AT1R gene polymorphism and long-term outcome in patients with heart failure

Offer Amir1, Ruthie E Amir, Hagar Paz

  • 1Heart Failure Center, Department of Cardiovascular Medicine, Lady Davis Carmel and Lin Medical Centers, Haifa, Israel.

Cardiology
|July 10, 2008
PubMed

Insights

The angiotensin II type 1 receptor (AT1R) CC genotype is linked to worse outcomes in heart failure (HF) patients, including increased mortality. This suggests potential for genome-based HF therapies.

Area of Science:

  • Cardiovascular Genetics
  • Heart Failure Pathophysiology
  • Pharmacogenomics

Background:

  • Angiotensin II is crucial in heart failure (HF) development.
  • The angiotensin II type 1 receptor (AT1R) is a key mediator of Angiotensin II effects.
  • Genetic variations in AT1R may influence HF prognosis.

Purpose of the Study:

  • To investigate the AT1R A1166C polymorphism in systolic HF patients.
  • To correlate AT1R genotype with clinical characteristics and outcomes.
  • To assess the prognostic value of AT1R polymorphism in HF.

Main Methods:

  • Genotyping of 134 HF patients for AT1R A1166C using PCR-RFLP.
  • Analysis of clinical, ECG, echocardiographic, and lab parameters.
  • Long-term survival analysis (30 months) based on AT1R genotype.

Main Results:

  • AT1R 1166C allele and CC genotype frequencies were similar to the general population.
  • The CC genotype was associated with ischemic HF etiology (p=0.02).
  • CC genotype correlated with advanced disease, renal dysfunction (p=0.008), and significantly higher mortality (p=0.008).

Conclusions:

  • The CC AT1R genotype is a marker for poor prognosis in HF.
  • Increased mortality risk was observed in AT1R CC homozygous patients.
  • Findings support the development of genome-based therapies for HF.
Abstract

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Heart Failure Drugs: β-Blockers01:22

Heart Failure Drugs: β-Blockers

β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation, vasodilation, and...