AGTR1

The AGTR1 gene encodes the type 1 angiotensin II receptor, a critical component of the cardiovascular system that regulates blood pressure and fluid balance. 

This receptor is primarily responsible for the vascular and renal actions of angiotensin II, influencing cardiovascular homeostasis and contributing to the pathology of heart diseases and hypertension. 

AGTR1 is widely expressed in key tissues such as the liver, lungs, and adrenal glands, and its role extends to cellular functions in cardiac hypertrophy and arrhythmias. 

Pharmacologically, it is targeted by medications like Losartan to manage hypertension and heart failure effectively.  Additionally, emerging gene therapies aimed at AGTR1 show potential in treating hypertension in animal models, underscoring its pivotal role in cardiovascular health and disease.

Understanding AGTR1: What is AGTR1?  [1., 4.]

The AGTR1 gene encodes the type 1 receptor for angiotensin II, a crucial hormone regulating blood pressure and volume in the cardiovascular system.  This receptor mediates the primary cardiovascular effects of angiotensin II.

 Initially, it was believed that there were two types of receptors, AGTR1A and AGTR1B, but further research suggested that there is only one type 1 receptor gene in humans, with alternative splicing leading to multiple transcript variants.

Expression studies have shown that AGTR1 is active in various human tissues, including the liver, lung, adrenal glands, and adrenocortical adenomas.  Its expression is essential for maintaining cardiovascular homeostasis. 

Research has revealed that AGTR1 plays a role in cardiac hypertrophy and arrhythmias following myocardial ischemia.

Pharmacologically, agents that target AGTR1 have proven effective in treating hypertension and heart failure.  Losartan, an AGTR1 antagonist, has shown efficacy without significant side effects. 

Additionally, gene therapy targeting AGTR1 has demonstrated promise in reducing blood pressure in animal models of hypertension.

Studies in animal models, particularly mice, have provided insights into the physiological and pathological roles of AGTR1.  

Knockout and transgenic mouse models have elucidated the receptor's involvement in vascular biology, cardiac hypertrophy, and renal function regulation.  Notably, the absence or malfunction of AGTR1 has been linked to conditions such as hypertension, cardiac fibrosis, and renal tubular dysgenesis.

Moreover, research has highlighted the intricate interactions between AGTR1 and other signaling pathways.  For instance, AGTR1 can form heterodimers with the bradykinin B2 receptor, influencing G protein activation and signaling pathways. 

Additionally, microRNA regulation of AGTR1 expression has been identified, suggesting a post-transcriptional mechanism for modulating its activity.

Overall, AGTR1 is a pivotal player in the renin-angiotensin system, exerting significant effects on cardiovascular physiology and pathology.  Understanding its molecular mechanisms and interactions provides valuable insights into the development of therapeutic strategies for cardiovascular diseases.

Biological Function and Role of the AGTR1 Receptor in the Renin-Angiotensin System  [6.]

AGTR1 is predominantly expressed in vascular smooth muscle cells, the heart, and the kidneys, where it binds angiotensin II, initiating a cascade of biochemical events that influence vascular tone, sodium retention, and blood pressure.

The AGTR1 receptor, a member of the G protein-coupled receptor (GPCR) family, activates multiple intracellular signaling pathways upon AngII binding.  

Besides its G protein (Gq/11) coupling leading to vasoconstriction and fluid balance regulation, the AGTR1 receptor can also engage various other signaling pathways, including tyrosine kinases and mitogen-activated protein kinases (MAPKs). 

These pathways are crucial for vascular and tissue remodeling observed in cardiovascular diseases.

Regulation of the AGTR1 receptor function involves phosphorylation and internalization processes mediated by G protein-coupled receptor kinases (GRKs) and arrestins.  

GRKs phosphorylate the receptor, initiating receptor desensitization and internalization. 

Arrestins bind phosphorylated receptors, promoting internalization and subsequent signaling cascades.

How AGTR1 Contributes to Cardiovascular Regulation and Its Implications in Pathological Conditions  [3.]

The role of AGTR1 extends into pathological states such as hypertension, where overactivity of the receptor contributes to elevated blood pressure and the subsequent risk of cardiovascular diseases. 

In heart failure, the enhanced stimulation of AGTR1 leads to adverse remodeling processes and cardiac dysfunction.  

The understanding of AGTR1's role in these conditions is crucial for the development of targeted therapies that inhibit its overactivation, such as angiotensin receptor blockers (ARBs), which are commonly used to treat hypertension and heart failure.

Overview of Diseases Linked to AGTR1 Alterations

Genetic variations and polymorphisms in the AGTR1 gene have been associated with an increased susceptibility to various cardiovascular disorders, including myocardial infarction and renal pathologies. 

The gene for the AGTR1 protein may contain alterations or mutations that cause increase or decrease of function of the AGTR1 protein.  

Testing for genetic alterations in the form of SNPs is increasingly available and can shed light on an individual’s potential for health and disease.  

What is a SNP?

A SNP, or single nucleotide polymorphism, refers to a variation at a single position in a gene along its DNA sequence.  A gene encodes a protein, so an alteration in that gene programs the production of an altered protein.  

As a type of protein with great functionality in human health, alterations in genes for enzymes may confer a difference in function of that enzyme.  The function of that enzyme may be increased or decreased, depending on the altered protein produced.  

SNPs are the most common type of genetic variation in humans and can occur throughout the genome, influencing traits, susceptibility to diseases, and response to medications.

The completion of the Human Genome Project has significantly expanded opportunities for genetic testing by providing a comprehensive map of the human genome that facilitates the identification of genetic variations associated with various health conditions, including identifying SNPs that may cause alterations in protein structure and function.  

Genetic testing for SNPs enables the identification of alterations in genes, shedding light on their implications in health and disease susceptibility.

SNPs Associated with Alterations in AGTR1 Function

AGTR1 rs5186  [2.] 

The AGTR1 rs5186 SNP is associated with alterations in AGTR1 function that increase angiotensin II levels, potentially affecting mRNA stability and transcription. These alterations are linked to increased blood pressure and a higher risk of developing essential hypertension, particularly in individuals with the CC genotype. 

This mutation may lead to upregulation of the AGTR1 receptor, enhancing its pathophysiological effects on vasoconstriction and sodium and water reabsorption.

Laboratory Testing for AGTR1

Genetic testing for single nucleotide polymorphisms (SNPs) typically involves obtaining a sample of DNA which can be extracted from blood, saliva, or cheek swabs. 

The sample may be taken in a lab, in the case of a blood sample.  Alternatively, a saliva or cheek swab sample may be taken from the comfort of home. 

Test Preparation

Prior to undergoing genetic testing, it's important to consult with a healthcare provider or genetic counselor to understand the purpose, potential outcomes, and implications of the test.  This consultation may involve discussing medical history, family history, and any specific concerns or questions. 

Additionally, individuals may be advised to refrain from eating, drinking, or chewing gum for a short period before providing a sample to ensure the accuracy of the test results.  Following sample collection, the DNA is processed in a laboratory where it undergoes analysis to identify specific genetic variations or SNPs. 

Once the testing is complete, individuals will typically receive their results along with interpretation and recommendations from a healthcare professional. 

It's crucial to approach genetic testing with proper understanding and consideration of its implications for one's health and well-being.

Patient-Centric Approaches

A patient-centered approach to SNP genetic testing emphasizes individualized medicine, tailoring healthcare decisions and interventions based on an individual's unique genetic makeup.

When that is combined with the individual’s health status and health history, preferences, and values, a truly individualized plan for care is possible. 

By integrating SNP testing into clinical practice, healthcare providers can offer personalized risk assessment, disease prevention strategies, and treatment plans that optimize patient outcomes and well-being. 

Genetic testing empowers a deeper understanding of genetic factors contributing to disease susceptibility, drug response variability, and overall health, empowering patients to actively participate in their care decisions. 

Furthermore, individualized medicine recognizes the importance of considering socioeconomic, cultural, and environmental factors alongside genetic information to deliver holistic and culturally sensitive care that aligns with patients' goals and preferences. 

Through collaborative decision-making and shared decision-making processes, patients and providers can make informed choices about SNP testing, treatment options, and lifestyle modifications, promoting patient autonomy, engagement, and satisfaction in their healthcare journey.

Genetic Panels and Combinations

Integrating multiple biomarkers into panels or combinations enhances the predictive power and clinical utility of pharmacogenomic testing. Biomarker panels comprising a variety of transporter proteins and enzymes including drug metabolizing enzymes offer comprehensive insights into individual drug response variability and treatment outcomes. 

Combining genetic SNP testing associated with drug transport, metabolism, and pharmacodynamics enables personalized medicine approaches tailored to individual patient characteristics and genetic profiles.

Biomarkers Related to AGTR1

Renin and Angiotensin II: Their Roles in Relation to AGTR1 and How They Are Measured

Renin, an enzyme responsible for the conversion of angiotensinogen to angiotensin I, and angiotensin II, the primary effector molecule of the renin-angiotensin system, are directly linked to the function of AGTR1. 

Measuring the levels of these molecules provides insights into the overall activity of the renin-angiotensin system. Laboratory tests typically measure plasma renin activity (PRA) to assess the rate at which angiotensin I is produced from angiotensinogen. 

Similarly, angiotensin II levels can be quantified using immunoassays that gauge its concentration in the blood, offering an indication of the system's output that directly impacts AGTR1 activity.

Aldosterone: Its Interaction with AGTR1 and Methods for Clinical Measurement

Aldosterone, a steroid hormone released by the adrenal cortex, plays a critical role in sodium retention and potassium excretion, processes that are modulated by AGTR1 activation. 

The measurement of aldosterone levels is particularly important in patients with suspected hyperaldosteronism or when assessing the efficacy of treatments targeting AGTR1, such as those using angiotensin receptor blockers. 

Aldosterone levels are typically measured through blood tests, and the aldosterone-to-renin ratio (ARR) is used to screen for conditions like primary aldosteronism, offering valuable data on the interaction between aldosterone and AGTR1.

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs.