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Postural Orthostatic Tachycardia Syndrome (POTS): Genetics, Causes, Symptoms, and Management Strategies

Key takeaways:
~ POTS (postural orthostatic tachycardia syndrome) is a problem with how your autonomic nervous system regulates heart rate, causing it to increase suddenly when standing.
~ There are several different triggers or causes for POTS.
~ Genetic variants can make you more susceptible to the condition, and understanding your genes can help you target the right therapy.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today

Postural Orthostatic Tachycardia Syndrome (POTS): Background Science, Dysautonomia

Do you feel lightheaded when you stand? Does your heart suddenly race? POTS (postural orthostatic tachycardia syndrome) is a problem with how your autonomic nervous system regulates heart rate. POTS can also cause fatigue, brain fog, shaking, and other symptoms, in addition to lightheadedness when standing up.

Doctors define POTS as:

  • an increase in heart rate of 30 BPM (beats per minute) within the first 10 minutes of standing
  • Or an increase in heart rate to over 120 BMP within the first 10 minutes of standing[ref]

These requirements define POTS as long as the person doesn’t have orthostatic hypotension (a condition where blood pressure initially drops when standing).

For teens and kids, most doctors now define POTS as a heart rate increase of over 40 BPM.

Millions of people around the world have POTS. The Dysautonomia International website explains that POTS impacts 1 to 3 million Americans.

POTS Symptom Checklist:

Symptoms that often go along with POTS include[ref][ref][ref][ref]:

✓ fatigue
✓ headaches, brain fog
✓ lightheaded, fainting, vertigo
✓ heart palpitations, chest pain
✓ exercise intolerance
✓ shaking, cold hands and feet
✓ abdominal pain, nausea, bloating
✓ diarrhea, constipation, bladder problems

Cause of POTS (Postural Orthostatic Tachycardia Syndrome):

POTS is a syndrome – meaning a collection of symptoms – rather than a specific disease. Thus there are a variety of diseases or chronic conditions that can cause POTS symptoms.

Diseases and conditions linked to triggering POTS include:

  • Autoimmune activation of the adrenergic system[ref][ref]
  • Autoimmune activation of the angiotensin II type 1 receptor[ref]
  • Mast cell activation[ref]
  • Viral illness, infections[ref]
  • Joint hypermobility (found in about 50% of teens with POTS), Ehlers-Danlos[ref][ref]
  • linked to the HPV vaccine (more studies are needed on this to show causality)[ref]
  • Concussions[ref]
  • Surgery, bed rest[ref]
  • Inflammatory disorders[ref]

POTS is often made worse by heat stress.

From lying down to standing up: blood pressure and heart rate

When someone who does not have POTS gets out of bed and stands up, the body goes through a series of regulatory changes that alter heart rate. Because blood pressure and heart rate regulation are automatic, we aren’t even aware that they are taking place.

Upon standing, gravity causes blood to go from the chest to the lower abdomen and legs. Within the first 30 seconds of standing, there is a fluid shift between the blood vessels and the space in between the cells.

This change in blood volume causes receptors in the heart to be activated and alters the heart’s stroke volume.

All of this causes the heart rate to increase just a little bit normally. It also alters blood pressure slightly (decreased systolic BP, increased diastolic BP).[ref]

Thus, when standing up, a slight increase in heart rate and BP is normal.

What happens when a person with POTS stands up?

There are a couple of different scenarios of what is happening in people with POTS (more details below). But generally, POTS can be caused by low blood volume or by the blood vessels in the legs not constricting enough.[ref]

If the person with POTS is hypovolemic – reduced blood volume – they usually have an elevated heart rate even when at rest. This heart rate elevation worsens upon sitting or standing, and the heart rate increases substantially.

For someone with reduced vasoconstriction in the legs, the heart rate increases dramatically to maintain normal blood pressure. This increase could be worsened in high-heat conditions, causing more blood to flow to the skin.[ref]

Autonomic nervous system, blood regulation:

Dysautonomia is a term you will often see when reading about POTS. Essentially, dysautonomia means a dysfunction of the autonomic nervous system. It is a catch-all term, with several chronic conditions falling under the umbrella of dysautonomia.[ref]

The autonomic nervous system controls involuntary functions in the body – including heart rate, blood pressure, and the motility of the digestive tract.

The body tightly regulates blood pressure through the renin-angiotensin-aldosterone system. It balances out the volume of blood by regulating sodium. In the kidneys, this system can either increase sodium reabsorption or water reabsorption to alter blood volume in the body.[ref]

Think about osmosis from science class — changing the amount of water through a membrane due to how much salt is on one side of the membrane. The kidneys regulate sodium concentration to regulate fluid in this same way.

Angiotensin system and POTS:
When the renin-angiotensin-aldosterone system is involved in causing POTS, there can be an increase in plasma angiotensin II. This increase causes an imbalance in blood volume due to the kidneys not retaining enough sodium. Additionally, some researchers have found that there is inadequate ACE2 activity.[ref][ref]

Vasoconstriction and POTS:
Some people with POTS have issues with the sympathetic nervous system not working correctly in the feet and legs. When standing up, it can result in insufficient vasoconstriction (e.g., blood vessels are too relaxed). As a result, blood pools in legs and feet, as well as the abdominal cavity. The lack of vasoconstriction and the pooling blood then kicks the heart into high gear, pumping hard to make up for the lack of blood flow.[ref]

Sympathetic nervous system, NET, medications, and POTS: Hyperadrenergic

One branch of the autonomic nervous system is the sympathetic nervous system (fight-or-flight response).

The activation of the sympathetic nervous system releases norepinephrine. Norepinephrine (aka noradrenaline) functions as a neurotransmitter and a stress hormone in the body.

Adrenergic system and POTS: 
A subset of people with POTS have what is known as the ‘hyperadrenergic’ form. When these people stand, their bodies release an excess of norepinephrine. It can cause heart palpitations, tremors, rapid heartbeat, feeling anxious, and increased blood pressure. Some patients with hyperadrenergic POTS also get headaches upon standing.[ref][ref]

Alternatively, instead of releasing excess norepinephrine, the body may not clear out the normal norepinephrine quickly enough. Or both could occur together.

Norepinephrine transporter:
Alterations in the norepinephrine transporter (NET) can cause reduced clearance of norepinephrine, leaving the sympathetic nervous system in a state of excessive activation. Rare mutations and more common gene variants that code for NET (norepinephrine transporter) are linked to POTS. Additionally, certain medications are NET inhibitors – some tricyclic antidepressants and certain ADHD medications.[ref]

For example, atomoxetine (Strattera) is an ADHD medication that targets the norepinephrine transporter. In a clinical trial, it has been shown to significantly increase the standing heart rate in POTS patients.[ref]

Autoimmunity causing POTS:

What could cause either the regulation of blood volume or the adrenergic (norepinephrine) system to go haywire?

Research shows that for many people, POTS can be due to an autoimmune attack on either the adrenergic system or the renin-angiotensin system.[ref][ref] Both systems are important in heart rate and blood flow.

For example, a small study in 2018 found that most patients with POTS in their study had angiotensin II type 1 receptor antibodies (IgG) as well as adrenergic activation, showing an autoimmune activation of that receptor. Interestingly, losartan, a commonly used hypertension medication that acts on the angiotensin II receptor, reduced the receptor activity down to the same levels as the control.[ref]

Another recent study (Aug. 2020) showed that patients with POTS were likely to have autoimmune activity towards the adrenergic receptors1 receptor, β2 receptor, cholinergic, and opioid receptor-like 1).[ref]

Is POTS Genetic?

Genetic mutations and POTS:

There is no one specific gene mutation that causes POTS. Rather, POTS is a syndrome that can have its genetic roots in various genes. Understanding where your genetic susceptibility lies may help you find your best treatment options.

For many people, an autoimmune condition (adrenergic system, angiotensin II receptor) triggers POTS.

The HLA genes code for an important part of our adaptive immune system. They help the body understand what is foreign (bacteria, viruses) and needs to be attacked. They also help the body understand which tissue is ‘self’ and should be left alone by the immune system.

Quite a few autoimmune diseases are linked to having different variants in the HLA genes. This HLA gene variation makes the human population resilient to lots of different and new pathogens, but this variation also makes individuals more susceptible to autoimmune disease.

However, one of the biggest risk factors is an HLA variant that is not included in 23andMe or AncestryDNA data. A study in 2019 identified the HLA-DQB1*0609 serotype as increasing the risk of POTS by over 8-fold![ref]

Other genetic variants increase susceptibility to POTS in different ways. The genes that have been identified so far by researchers include nitric oxide genes, norepinephrine (noradrenaline) transporters, and the beta2-adrenergic receptor – all of which impact blood volume regulation. (see the Genetic Variants section below).

Epigenetics and POTS:

Epigenetics refers to alterations in how the genetic code is turned on or off for translation. In a nutshell, the nucleus of every cell contains the complete genome, but only certain genes remain essential for that cell to function. Epigenetic markers control how often a gene is translated into its protein.

Studies showed that people with POTS were more likely to have epigenetic modifications that reduced the function of the norepinephrine transporter (SLC6A2 gene).[ref][ref]

It goes hand-in-hand with the research showing that people with genetic variants that reduce the function of the SLC6A2 gene are also more susceptible to POTS. (See genetics section below).

Triggers of POTS:

Researchers have identified several different triggering events that can initiate POTS.

Vaccines and POTS:

One trigger for POTS for some individuals seems to be certain vaccines. For example, there are dozens of case reports of POTS shortly following the HPV vaccine. Additionally, several studies followed a number of women after the HPV shot, finding an increase in dysautonomia and POTS.[ref][ref][ref][ref][ref]

Why would an HPV vaccine cause POTS in a minority of people? Some researchers point to an autoimmune response (adrenergic receptor antibodies) due to molecular mimicry with specific HPV peptides.[ref]

There are, of course, a lot of unanswered questions on the links between the HPV vaccine and POTS. Epidemiological studies often don’t find a statistical, population-wide link between the introduction of the HPV virus and the number of POTS diagnoses.[ref][ref] Additionally, some researchers point to media coverage as a cause for any post-vaccination symptom spikes.[ref]


Interestingly, one of the mechanisms that cause POTS is a disturbance in the renin-angiotensin system, possibly due to inadequate ACE2 activity.[ref] A study of 38 people with POTS had lower ACE2 activity than the healthy control group.[ref]

Researchers discovered early on (Aug. 2020) that the SARS-CoV-2 virus may cross-react with autoimmune target proteins. The researchers caution that people who have had Covid may be at an increased risk for autoimmune conditions.[ref]

  • A case series that included 20 patients explained that POTS is a common autonomic disorder following Covid.[ref]
  • POTS is also common in people with long Covid.[ref]
  • POTS is common enough in long Covid to have it now characterized as one of the defined subtypes.[ref]


POTS Genotype Report

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Lifehacks for POTS: Diet, supplements, apps, and treatments

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Anjum, Ibrar, et al. “Postural Orthostatic Tachycardia Syndrome and Its Unusual Presenting Complaints in Women: A Literature Minireview.” Cureus, vol. 10, no. 4, p. e2435. PubMed Central, Accessed 12 Apr. 2022.

Bayles, Richard, et al. “Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 8, Aug. 2012, pp. 1910–16. PubMed,

Blitshteyn, Svetlana, et al. “Autonomic Dysfunction and HPV Immunization: An Overview.” Immunologic Research, vol. 66, no. 6, Dec. 2018, pp. 744–54. PubMed,

Bonamichi-Santos, Rafael, et al. “Association of Postural Tachycardia Syndrome and Ehlers-Danlos Syndrome with Mast Cell Activation Disorders.” Immunology and Allergy Clinics of North America, vol. 38, no. 3, Aug. 2018, pp. 497–504. PubMed,

Boris, Jeffrey R., and Thomas Bernadzikowski. “Demographics of a Large Paediatric Postural Orthostatic Tachycardia Syndrome Program.” Cardiology in the Young, vol. 28, no. 5, May 2018, pp. 668–74. PubMed,

Brinth, Louise, et al. “Suspected Side Effects to the Quadrivalent Human Papilloma Vaccine.” Danish Medical Journal, vol. 62, no. 4, Apr. 2015, p. A5064.

Brinth, Louise S., et al. “Orthostatic Intolerance and Postural Tachycardia Syndrome as Suspected Adverse Effects of Vaccination against Human Papilloma Virus.” Vaccine, vol. 33, no. 22, May 2015, pp. 2602–05. PubMed,

Bryarly, Meredith, et al. “Postural Orthostatic Tachycardia Syndrome: JACC Focus Seminar.” Journal of the American College of Cardiology, vol. 73, no. 10, Mar. 2019, pp. 1207–28. ScienceDirect,

Chandler, Rebecca E., et al. “Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase®.” Drug Safety, vol. 40, no. 1, Jan. 2017, pp. 81–90. PubMed,

Dysautonomia International: Dysautonomia Awareness, Dysautonomia Advocacy, Dysautonomia Advancement. Accessed 12 Apr. 2022.

Dysautonomia International: Postural Orthostatic Tachycardia Syndrome. Accessed 12 Apr. 2022.

Fedorowski, Artur, et al. “Antiadrenergic Autoimmunity in Postural Tachycardia Syndrome.” Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, vol. 19, no. 7, July 2017, pp. 1211–19. PubMed,

Fountain, John H., and Sarah L. Lappin. “Physiology, Renin Angiotensin System.” StatPearls, StatPearls Publishing, 2022. PubMed,

Garland, Emily M., et al. “Endothelial NO Synthase Polymorphisms and Postural Tachycardia Syndrome.” Hypertension (Dallas, Tex.: 1979), vol. 46, no. 5, Nov. 2005, pp. 1103–10. PubMed,

Green, Elizabeth A., et al. “Effects of Norepinephrine Reuptake Inhibition on Postural Tachycardia Syndrome.” Journal of the American Heart Association, vol. 2, no. 5, Sept. 2013, p. e000395. (Crossref),

Ikeda, Shu-Ichi, et al. “Suspected Adverse Effects after Human Papillomavirus Vaccination: A Temporal Relationship.” Immunologic Research, vol. 66, no. 6, Dec. 2018, pp. 723–25. PubMed,

Kanjwal, Khalil, et al. “Clinical Presentation and Management of Patients with Hyperadrenergic Postural Orthostatic Tachycardia Syndrome. A Single Center Experience.” Cardiology Journal, vol. 18, no. 5, 2011, pp. 527–31. PubMed,

Khan, Abdul Waheed, et al. “NET Silencing by Let-7i in Postural Tachycardia Syndrome.” JCI Insight, vol. 2, no. 6, Mar. 2017, p. e90183. PubMed,

Li, Hongliang, et al. “Autoimmune Basis for Postural Tachycardia Syndrome.” Journal of the American Heart Association, vol. 3, no. 1, Feb. 2014, p. e000755. PubMed,

Marques, F. Z., et al. “A Polymorphism in the Norepinephrine Transporter Gene Is Associated with Affective and Cardiovascular Disease through a MicroRNA Mechanism.” Molecular Psychiatry, vol. 22, no. 1, Jan. 2017, pp. 134–41. PubMed,

Miranda, Nicole A., et al. “Activity and Exercise Intolerance After Concussion: Identification and Management of Postural Orthostatic Tachycardia Syndrome.” Journal of Neurologic Physical Therapy, vol. 42, no. 3, July 2018, pp. 163–71. PubMed Central,

Mustafa, Hossam I., et al. “Abnormalities of Angiotensin Regulation in Postural Tachycardia Syndrome.” Heart Rhythm, vol. 8, no. 3, Mar. 2011, pp. 422–28. PubMed,

Nakao, Ryota, et al. “GNB3 C825T Polymorphism Is Associated with Postural Tachycardia Syndrome in Children.” Pediatrics International: Official Journal of the Japan Pediatric Society, vol. 54, no. 6, Dec. 2012, pp. 829–37. PubMed,

Raj, Satish R. “The Postural Tachycardia Syndrome (POTS): Pathophysiology, Diagnosis & Management.” Indian Pacing and Electrophysiology Journal, vol. 6, no. 2, Apr. 2006, pp. 84–99. PubMed Central,

Segal, Yahel, and Yehuda Shoenfeld. “Vaccine-Induced Autoimmunity: The Role of Molecular Mimicry and Immune Crossreaction.” Cellular and Molecular Immunology, vol. 15, no. 6, June 2018, pp. 586–94. PubMed Central,

Shibao, Cyndya, et al. “Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders.” Hypertension (Dallas, Tex.: 1979), vol. 45, no. 3, Mar. 2005, pp. 385–90. PubMed,

Skufca, J., et al. “Incidence Rates of Guillain Barré (GBS), Chronic Fatigue/Systemic Exertion Intolerance Disease (CFS/SEID) and Postural Orthostatic Tachycardia Syndrome (POTS) Prior to Introduction of Human Papilloma Virus (HPV) Vaccination among Adolescent Girls in Finland, 2002–2012.” Papillomavirus Research, vol. 3, Mar. 2017, pp. 91–96. PubMed Central,

Stewart, Julian M., et al. “Defects in Cutaneous Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Production in Postural Tachycardia Syndrome.” Hypertension, vol. 53, no. 5, May 2009, pp. 767–74. (Atypon),

Thomsen, Reimar Wernich, et al. “Hospital Records of Pain, Fatigue, or Circulatory Symptoms in Girls Exposed to Human Papillomavirus Vaccination: Cohort, Self-Controlled Case Series, and Population Time Trend Studies.” American Journal of Epidemiology, vol. 189, no. 4, Apr. 2020, pp. 277–85. PubMed Central,

Vojdani, Aristo, and Datis Kharrazian. “Potential Antigenic Cross-Reactivity between SARS-CoV-2 and Human Tissue with a Possible Link to an Increase in Autoimmune Diseases.” Clinical Immunology (Orlando, Fla.), vol. 217, Aug. 2020, p. 108480. PubMed Central,

Yu, Xichun, et al. “Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome.” Journal of the American Heart Association, vol. 7, no. 8, Apr. 2018, p. e008351. PubMed,

Zhang, Qingyou, et al. “Clinical Features of Hyperadrenergic Postural Tachycardia Syndrome in Children: Hyperadrenergic POTS.” Pediatrics International, vol. 56, no. 6, Dec. 2014, pp. 813–16. (Crossref),

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.