Gout is often thought to be the “disease of kings” due to its association with gluttony and alcohol consumption. This stigma has prevented us from exploring its root cause for many years. Research in the last decade suggests the cause of gout is a lot more genetics than just diet. Gout can affect anyone, but if you have an affected first-degree family member, your risk increases by 2.5x! This begs the answer to the question, “Is gout hereditary?” While we attempt to discuss this, we’ll also touch upon how to learn your risk for gout via a genetic test.
Did You Know?
Many chronic conditions like diabetes, hypertension, or gout are influenced by many gene changes. Each change adds to the risk of developing the condition. You can learn your risk for these conditions as well as recommendations to lower your risk using your existing ancestry test DNA data.
Learn How.
Understanding Gout
Gout is one type of arthritis that results in inflammation, tenderness, and redness of one or more joints (ankles, wrists, fingers, and knees), most frequently the big toe joint.
People with gout have high levels of a chemical compound called urate or uric acid in their blood (hyperuricemia).
Uric acid is formed when purines break down, which are found naturally in the body.
Purines are substances obtained from certain seafood and meat.
Alcoholic beverages and sweetened drinks also increase uric acid in the blood.
Generally, uric acid dissolves in the blood and is excreted by the kidneys through the urine.
But sometimes, the body produces excess uric acid, or the kidneys excrete too little uric acid.
During this stage, uric acid builds up, and forms sharp, needle-like structures called urate crystals that accumulate in joints, and the immune system reacts by causing inflammation.
Types of Gout
Gout can be classified into two types based on the source of accumulation of uric acid:
- Primary gout
- Secondary gout
Primary gout is due to overproduction or under-excretion of uric acid.
It is because of factors like dietary excess, excessive alcohol consumption, and metabolic syndrome.
Secondary gout is due to medications that induce hyperuricemia while treating myeloproliferative diseases.
Secondary gout is mostly a result of the comorbidity of such diseases.
Symptoms of Gout
Gout sufferers frequently experience sudden, excruciating pain attacks that start at night and last for up to 12 hours.
This extreme discomfort, which usually begins at night, is a significant symptom of gout.
Most people only have pain in one particular joint. Your big toe is commonly where it starts, although it can happen anywhere.
Other gout symptoms include:
- Restricted movement of joints
- Redness, stiffness, and swelling in joints
- Long-lasting pain for days or weeks
Is Gout Hereditary?
With a strong genetic influence, gout is a condition that can be inherited. The heritability of gout is 65%!
Although there’s no clear inheritance pattern, studies suggest that having a close affected family member can increase your risk significantly.
An estimated 20% of gout sufferers have a relative with the condition.
To explore the heritability of gout, a group of researchers analyzed 4.2 million families.
Study Observations
- They discovered strong evidence that gout runs in families with higher risks for those with first- and second-degree relatives with the condition.
- The study further identified that the risk keeps increasing for every additional first-degree relative affected with gout.
- The risk is exorbitant (8-fold increase) when there’s an affected identical twin compared to a 2-fold increase for an affected biological parent/offspring.
Important Genes Underlying Gout
A meta-analysis published in 2018 suggests that the impact of genes on gout was much more significant than that of diet.
The study was done on 16,760 individuals with European ancestry.
They were exposed to several food items, some of which increased serum urate levels and others that it.
The researchers observed that diet only contributed to ≤0.3% of the variance in urate levels; by contrast, genetics contributed to a whopping 23.9% of the variance!
Genes that produce proteins that are responsible for urate transport play a prominent role in gout.
Urate transporters mediate urate excretion.
A variation in one of these urate-related genes may cause gout.
The genes that have so far been identified to have the strongest association with gout include
- Solute carrier family 2 member 9 (SLC2A9)
- Adenosine triphosphate (ATP) binding cassette subfamily G member 2 (ABCG2)
SLC2A9 Gene and Gout
The SLC2A9 gene produces a protein called GLUT-9 found in the kidneys.
This protein regulates the reabsorption of urate from the urine back into the blood.
It also assists in the removal of urate through urine.
A mutation in the SLC2A9 gene may result in increased urate reabsorption or decreased urate excretion.
This could lead to hyperuricemia and, eventually, gout.
ABCG2 Gene and Gout
The ABCG2 gene produces a multifunctional transporter protein called ABCG2, primarily in the stomach and liver.
The protein regulates the excretion of urate via stools (or poop).
If the ABCG2 gene is altered, the protein won’t be able to release urate into the intestines as it should.
As a result, urate excretion may decrease, increasing serum urate levels and leading to gout.
Who Is Prone To Gout? Risk Factors Explained
Now that we have seen that family history and genes play a vital role in gout risk let’s explore some of the other factors that can contribute to the risk.
- Sex at birth: Gout occurs more often in males as females naturally have lower uric acid levels. However, after menopause, the levels slowly start to match up to males’.
- Body weight: Being overweight or obese is a risk factor for gout. This is because obesity leads to excessive production of uric acid, which the kidneys struggle to eliminate.
- Certain medications: Some drugs like diuretics or ACE inhibitors promote water loss from the body via urine. However, this may cause uric acid buildup, increasing the risk of gout.
- Purine-rich foods: Inside the body, purine is converted into uric acid. Overconsumption of purine-rich foods like seafood and organ meats can thus increase gout risk.
- Alcohol consumption: When kidneys become too busy trying to excrete alcohol from the body, uric acid excretion becomes a second priority, which could lead to its buildup, ultimately resulting in gout.
Can Genetic Testing Predict The Likelihood Of Developing Gout?
At present, no genetic test can confirm with 100% accuracy whether or not you’ll get gout. But, it can really be helpful in understanding your risk for the condition.
These tests analyze commonly-associated genes with gout to identify the presence of genetic variants, if any.
If you possess a genetic variant, you may be at risk for gout.
You can then discuss the results with your doctor, who after considering your medical, family, and personal history, can recommend steps to lower your risk and prevent gout.
Xcode Life’s Gout DNA Report
Researchers have identified several genes associated with gout.
Xcode Life’s Gene Health report which analyzes your genetic risk for over 45+ health conditions, can help you understand your gout risk.
You can identify your genetic risk of gout by using your 23andMe (or any ancestry test) DNA data and placing an order for the Gene Health Report.
A Sample Gout DNA Report
Summary: Is Gout Hereditary?
- Gout is a prevalent and complicated form of arthritis that anyone can develop.
- A high level of uric acid in the blood (hyperuricemia) is the primary reason for gout.
- Extreme pain with redness, stiffness, and swelling in joints are the symptoms of gout.
- Studies have proven that gout runs in families and has a strong genetic association.
- Variations in the SLC2A9 and ABCG2 genes strongly influence the development of gout.
- Other risk factors include family history, gender, age, diet, medications, etc.
References
- https://medlineplus.gov/genetics/condition/gout/
- https://www.healthline.com/health/gout/is-gout-hereditary/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645862/
- https://www.sciencedaily.com/releases/2013/12/131202105034.htm
- https://www.mayoclinic.org/diseases-conditions/gout/symptoms-causes/syc-20372897
