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Genetic factors, not diet, are the prime drivers behind gout, study finds

The Gout by James Gillray
James Gillray, 1799
"The Gout" depicts the pain of the artist's podagra as a demon or dragon.

Until the 1980s, diet — particularly spicy foods — was considered a key cause of stomach ulcers (along with stress). Then we found out that these painful sores on the lining of the stomach were actually caused by a bacterium known as Helicobacter pylori (H. pylori), as well as by the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs).

For centuries, another ailment — gout — has also been blamed primarily on people’s dietary choices, particularly the “libertine excesses” (as the 18th-century poet William Cowper put it) of too much red meat and alcohol.

But that widely held belief is now being challenged. A study published earlier this week in the BMJ (formerly known as the British Medical Journal) has found that genes play a much, much larger role in the development of gout than diet.

This finding is important, for it may encourage more people with gout to seek medical treatment.

”People with gout often experience stigma from the societal misconception that gout is a condition caused by dietary habits and an unhealthy lifestyle, a view which is also pervasive among healthcare professionals and in portrayals of gout in lay media,” write Lorraine Watson and Eddy Roddy, two arthritis researchers at Keele University in Staffordshire, England, in an editorial that accompanies the study.

“As a result, patients known to have gout are often reluctant to seek help for fear that they will not be taken seriously or will be blamed for their lifestyle habits,” they add.

A common condition

Gout is a joint disease  — a form of arthritis — that causes swelling and extreme pain. It occurs when tiny, needle-like crystals consisting of a substance called uric acid build up in the joints, often beginning at the base of the big toe. Sometimes the crystals collect in the kidneys as well.

Uric acid normally dissolves in the blood and passes out of the body through urine, but in people with gout, uric acid levels become too high (a condition known as hyperuricemia), causing the painful crystals to accumulate.

Gout affects about 4 percent of American adults, or about 8.3 million individuals. The condition can strike anyone at any age, but it is most common among men over the age of 40. In fact, men are three times more likely to develop gout than women.

In past studies, certain foods — particularly meat, shellfish, alcohol and sugary soft drinks — have been linked to a higher risk of gout, while others  — fruit, vegetables, low-fat dairy products and coffee — have been associated with a lower risk.

But other research has shown that genetic factors play an important role in the development of the disease.

For the current study, researchers wanted to get a better understanding of the relative contribution of each factor — diet and genes — to the condition.

Study details

A team of researchers, led by Tanya Major, a post-doctoral fellow at the University of Otago in New Zealand, conducted a meta-analysis of data collected from 8,414 men and 8,346 women from five U.S. studies. All the participants were aged 18 or older, and none had kidney disease or gout. Nor were any of them taking prescription drugs known to affect uric acid levels (such as diuretics).

The data included genetic profiles and measurements of urate, an ionized form of uric acid that is present in blood. It also included the participants’ answers to detailed food questionnaires.

The meta-analysis found that high blood urate levels were associated with seven foods: beer, wine, liquor, potatoes, poultry, soft drinks and meat (beef, pork or lamb). Reduced blood urate levels were associated with eight foods: eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine and non-citrus fruit.

But each of those foods explained less than 1 percent of the variation in the participants’ urate levels.

The researchers then looked at the participants’ entire diets. They found that following any of three different healthy dietary guidelines (such as the DASH diet) was associated with lower urate levels, while following a diet high in unhealthy foods was linked with higher urate levels.

But, again, those diets explained less than 0.3 percent of the variation in the participants’ urate levels.

By contrast, when the researchers did their genetic analysis, they found that common genetic factors among the participants explained almost a quarter — 23.9 percent — of the variation in their urate levels.

These findings held even after the researchers adjusted for factors that can affect urate levels, such as age, body mass index (BMI), daily calorie intake, exercise habits and smoking status.

Limitations and implications

This meta-analysis comes with caveats. The five studies on which it was based used different food questionnaires, a factor that created some challenges when trying to combine the data for the analysis. In addition, all the American participants in the study were of European ancestry and none had gout, so the findings may not be generalizable to more ethnically diverse populations or to people diagnosed with the condition.

Still, the meta-analysis’ findings support other research involving twins and families that has suggested genetics explains at least 25 to 60 percent of the variability in blood urate levels.

“It came as no surprise to us that genetic factors have a larger influence on serum urate than dietary factors, what did surprise us was the magnitude of this difference, an almost 100-fold increase,” writes Major in a blog post for BMJ. “Overall diet explaining less than 0.5% of the variation in serum urate is a profoundly small influence considering that diet is so intrinsically associated with gout.”

“As this study was conducted in a ‘healthy population’ replication in a cohort of gout patients is necessary,” she adds. “[H]owever, for diet to explain so little of such an essential component in gout aetiology is an important finding. And if the follow-on analyses in gout patients find a similar difference in the magnitude of effect between genetics and diet this work will have provided me with an answer to those people asking “Gout, is that genetic?” A very definite yes. Gout is genetic, and “drinking too much beer” has very little influence on serum urate.”

For more imformation: You can read the study in full on the BMJ website.

Comments (2)

  1. Submitted by Greg Kapphahn on 10/12/2018 - 05:32 pm.

    I can’t help wonder two things:

    1) how long will it take for this to filter out to physicians (considering that there are still some who place their ulcer patients on bland diets),…

    and

    2) how does this change the treatment for gout – i.e. are there useful treatments for a genetic predisposition toward higher than normal serum uric acid levels?

    • Submitted by Alan Straka on 10/13/2018 - 11:25 am.

      This will not change the treatment of gout. It has been known for some time that gout is caused by the way the body manages the uric acid level. Diet can cause flare ups of the disease if you have it but is not itself the cause of the disease. The drug allopurinol is standard treatment to prevent flare ups while colchicine is given for flare ups. There are also newer drugs available if the standard treatment isn’t tolerated or does not manage the disease. There was some concern that allopurinol could damage the kidneys but that has recently been proven not to be the case. The drugs work well but sufferers still need to mind their diet.

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