Is Gout Hereditary? Understanding the Role of Genetics

Medically reviewed by David Ozeri, MD

Gout is a type of inflammatory arthritis characterized by sudden, severe attacks of pain and swelling. It occurs when uric acid, a waste product, builds up in the bloodstream, forming urate crystals in joints and tissues. These crystals trigger inflammation.

Diet and lifestyle factors can contribute to the development of hyperuricemia (high levels of uric acid in the bloodstream). But genetics also play a significant role.

Many genes are involved in uric acid production and excretion. Variations of these genes can affect uric acid levels and influence the risk of gout. But genes alone will not cause gout. Environmental factors like diet, obesity, smoking, and certain health conditions and medications must be present for gout to eventually develop.

This article will cover the link between gout and genetics, risk factors, genetic testing, and more.

What's the Link Between Gout and Genetics?

Genes involved in the development of gout include those that control uric acid production and excretion and that regulate immune function and inflammatory processes. The most common genes linked to gout are SLC2A9, ABCG2, and SLC22A12.

SLC2A9

The SLC2A9 gene regulates uric acid in the body. People with a SLC2A9 variant have higher levels of uric acid in their blood, increasing their risk of developing gout.

SLC2A9 encodes a protein involved in uric acid movement. Variations in this gene affect how effectively uric acid the body removes uric acid. SLC2A9 mutations are linked to hyperuricemia and gout in White, Chinese, and Polynesian people (among other groups). SLC2A9 also has greater effects in women, leading to higher than normal uric acid levels.

A Note on Gender and Sex Terminology

Verywell Health acknowledges that sex and gender are related concepts, but they are not the same. To reflect our sources accurately, this article uses terms like “female,” “male,” “woman,” and “man” as its sources do.

ABCG2

A second important gene in the development of gout is ABCG2. It plays a role in uric acid removal by the intestines, and ABCG2 gene mutations reduce the efficiency of this process. Variants of this gene impact people of African and Southeast Asian descent more frequently, and those populations may present with more severe symptoms of gout.

ABCG2 has also been found to reduce allopurinol's therapeutic response. Allopurinol is a medicine that reduces uric acid levels in the blood and urine of people with hyperuricemia. 

SLC22A12

Another significant gene involved in the development of gout is SLC22A12. It provides instructions for urate transporter 1 (URAT1), a protein found in the kidneys. The URAT1 protein helps urate absorption into the bloodstream or through urine excretion based on your body's needs.

SLC22A12 also helps transport molecules for urate, a by-product of chemical reactions in the body.

Mutations of SLC22A12 can increase or decrease uric acid levels. Research shows that 90% of hyperuricemia results from nonfunctional URAT mutations. Other variations of SLC22A12 can actually inhibit URAT1 and reduce gout risk.

What Percentage of People With Gout Have Relatives With the Condition?

Heritability is a measurement of genetic influence on illness and other traits passed down in families. Heritability does not guarantee that you will develop a condition; it just means you are more susceptible than others in the general population to a health condition that others in your family have.

The heritability rate for gout falls between 45% and 73%. Gout tends to affect multiple family members, and about 20% of people with gout will have family members with the condition. Your risk is even greater if you have a first-degree relative (a parent or sibling) with the condition.

Who Is Prone to Getting Gout?

Gout is the result of uric acid buildup in the body. Excess uric acid can enter the joints and cause urate crystals in the joints, which can trigger inflammation. When this happens, you may experience a gout attack that causes pain, swelling, redness, and stiffness in affected joints.

Certain risk factors, along with genetic disposition, can increase your risk of developing gout. Such risk factors include:

• Being an adult male between the ages of 30 and 50: Gout is more common in men than in premenopausal women, People who menstruate may develop gout after menopause.

• Being overweight: Studies suggest being overweight increases your chance of developing gout, and weight loss can reduce risk.

• Smoking: Though smoking does not directly cause gout, it can worsen symptoms. This is because cigarettes can increase uric acid levels. Smoking has also been linked to tophi, a complication of gout. Tophi are lumps of uric acid crystals that form around the joints and tissues affected by gout.

• Eating a diet high in purine-rich foods can lead to high uric acid levels. Purines are found in red meat, organ meats, seafood, alcohol, and sugary beverages.

• Having certain health conditions, such as high blood pressure, diabetes, kidney diseases, conditions that cause high cell turnover (psoriasis and some cancers), and rare genetic diseases that increase uric acid levels (i.e., Kelley-Seegmiller syndrome or Lesch-Nyhan syndrome)

• Taking certain medications, such as diuretics (water pills), aspirin, niacin (a B vitamin) in high amounts, and cyclosporine (an immunosuppressant)

If any of these risk factors apply to you, talk to your healthcare provider about how to reduce your risk.

Related: What Causes Gout?

Can Genetic Testing Predict the Likelihood of Gout?

Genetic testing examines an individual's DNA to determine their risk for developing a health condition. Testing can help identify genetic variations (alleles) that can increase a person's risk for gout. Alleles are copies of genes that influence hereditary characteristics.

The more risk variations a person has, the higher their risk for gout. One 2016 study found that having five or more risk alleles puts a person at a higher risk for gout than having four or fewer.

If your healthcare provider can identify specific gene variations that increase your risk for gout, they can use this information to guide treatment decisions. For example, they can prescribe medications that target specific genes that increase your risk for hyperuricemia.

Genetic testing can be helpful, but it has its limitations. Though it is possible to identify gene mutations linked to gout, these are not enough to predict the development of gout. Lifestyle factors and diet play a more significant role in the development of gout, and genetic testing alone is not enough to ascertain who will get gout or provide a full picture of gout risk.

How Is Gout Diagnosed?

A diagnosis of gout can be made based on your symptoms and the appearance of the affected joint. Your healthcare provider will also request additional testing to confirm gout or rule out other arthritis conditions. Tests may include:

• Joint aspiration test: With this test, the healthcare provider uses a needle to draw fluid from the gout-affected joint. The fluid is then examined under a microscope to look for urate crystals.

• Blood work: A uric acid blood test can measure uric acid levels in the blood, but blood tests are not enough to confirm gout. Other blood work might be done to check for inflammatory markers or proteins seen in other arthritis conditions, such as rheumatoid arthritis and psoriatic arthritis.

• Imaging: Joint X-rays might help rule out other causes of joint inflammation. Ultrasound and dual-energy computerized tomography (DECT) scans can detect urate crystals or tophi in the joints.

Related: How to Remove Gout Crystals From the Joint

What Are the Signs of Gout?

Some people with gout have asymptomatic hyperuricemia, the beginning state of gout in which uric acid builds up in the blood. This early stage does not cause symptoms, but uric acid levels will be elevated.

Hyperuricemia can become acute, with symptoms coming on quickly and suddenly. Gout attacks may last a few days and improve. Symptoms include intense joint pain, swelling, and warmth. Some people might also experience fever and chills.

Your next attack may not occur for a few months or even up to a year. If not managed, however, attacks can become more frequent and severe and last much longer.

If gout is not adequately treated, it can become chronic and lead to tophi. Tophi can cause permanent damage to joints.

How Is Gout Treated?

Untreated gout can become chronic and painful and cause joint damage and deformity. Fortunately, the condition is manageable and treatable. Your treatment plan will depend on the severity of your symptoms and how long you have had gout.

Medications

Medications can treat gout. Some work by relieving pain and reducing inflammation, while others help lower uric acid and prevent future attacks.

Medicines that can relieve gout pain include:

Medicines that can lower uric acid levels include:

• Xanthine oxidase inhibitors, such as Zyloprim (allopurinol) and Uloric (febuxostat)

• Probenecid to increase the filtering of uric acid by the kidneys

• Krystexxa (pegloticase): An intravenous medication taken to break down urate crystals.

If you have undergone genetic testing, your healthcare provider can prescribe medicines that target specific genes that cause hyperuricemia. These include xanthine oxidase inhibitors.

Lifestyle Changes

Along with medications, your healthcare provider will recommend lifestyle changes to alleviate symptoms and reduce the risk of future attacks.

Lifestyle changes to improve gout symptoms include:

• Reducing your alcohol consumption

• Quitting smoking

• Losing weight if you are overweight

• Avoiding foods and beverages that are high in purines.

Related: Arthritis Gout Foods to Eat and Avoid With Gout

Surgery

Surgery is rarely necessary to treat gout. However, surgery may be necessary to treat infected tophi, nerve compression, or joint damage.

Preventing Complications

Follow your treatment plan to prevent gout complications. Your healthcare provider can create a unique treatment plan for your particular health situation.

You should also see your healthcare provider regularly to review your symptoms and treatment plan. Your medical appointments are also a good time to express any concerns.

Can You Prevent Gout?

Because gout is a partly genetic condition, preventing it completely isn't possible. But you can do some things to reduce your risk for the condition.

Some ways to reduce your risk are to:

• Limit or avoid alcohol.

• Maintain a healthy weight.

• Manage health conditions such as kidney disease, diabetes, and high blood pressure.

• Eat a healthy and balanced diet.

If you think you are at a high risk of getting gout, speak to a healthcare provider. If you develop gout, they will start treatment right away to avoid complications.

Related: How to Prevent Gout

When to Contact a Healthcare Provider

If you experience sudden, severe joint pain, contact a healthcare provider. Untreated gout can lead to chronic gout and joint damage.

Seek immediate medical care if your joint is hot or inflamed or you have a fever. These might be signs of a bone or joint infection.

Summary

Gout is a type of inflammatory arthritis that tends to run in families. Familial genes involved in hyperuricemia and the development of gout include SLC2A9, ABCG2, and SLC22A12. Variations of these genes can affect uric acid production and excretion and regulation of immune function and inflammatory processes.

Genetic testing might help healthcare providers identify who might develop gout and how to facilitate treatment for those who go on to get the condition. But genes alone are not enough to lead to the development of gout. Environmental factors like diet and lifestyle play a more significant role in the development of the condition.

Reducing your genetic risk for gout is not possible. However, you can mitigate your risk for the condition by not smoking or drinking alcohol, avoiding a purine-rich diet, losing weight, and managing health conditions like diabetes, kidney disease, and high blood pressure.

Early diagnosis and treatment of gout are essential to reducing complications like tophi. If you experience symptoms of gout, including sudden, severe joint pain, you should let a healthcare provider know right away. They can assess you, determine the cause of your symptoms, and start you on a treatment plan.

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