Gout Caused by Genetics More Than Diet

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One of the most common misconceptions about gout, according to an article by the Arthritis Foundation, is that diet is the primary cause. Gout, or gouty arthritis, is a painful condition caused by a high level of uric acid in the blood that can lead to deposits of uric acid crystals in the joints and tissues. Most often gout affects the big toe joint, but it can also occur in the hands, feet, wrists, ankles, knees, and elbows.

Uric acid is formed in the body naturally when compounds called purines are broken down. Most uric acid (about two-thirds) is produced when our cells age and die, but about a third of uric acid in our bodies is produced by the breakdown of purines that are found in many foods and drinks. Among the most purine-rich foods and drinks are red meat, shellfish, alcoholic beverages (especially beer), and sugary drinks. People with gout typically try to avoid foods and drinks like these to try to lower the amount of uric acid in their bodies.

Various factors can contribute to elevated blood uric acid levels and the development of gout (e.g., joint damage, infection, medications, etc.) The goals of a recent study published in The BMJ was to test various foods for links to uric levels and to determine within a general population the extent to which diet contributes to uric acid levels compared to inherited genetic variations. Findings from the study suggest that, at least in a population without gout, genetics play a much larger role than diet in promoting high uric acid levels in the blood.

Importantly, the recognition of a significant genetic component to this condition may help reduce the stigmatization and embarrassment that some people have due to a condition that many see as self-inflicted and the result of unhealthy lifestyle habits. The hope is that this new information may help empower those people with gout who have been reluctant to seek help.

According to an accompanying editorial, the new research “provides important evidence that much of patients’ preponderance to [high uric acid levels] and gout is [genetic and] non-modifiable, countering these harmful but well-established views and practices.”

The researchers collected and analyzed data from 8,414 men and 8,346 women of European ancestry from five ongoing population-based cardiovascular and nutrition studies in the United States. Participants were excluded from this study if they had kidney disease or gout, or if they were taking uric acid-lowering drugs or diuretic drugs (water pills). The participants filled out dietary surveys, had their blood uric acid levels measured, and underwent genetic testing.

By comparing the participants’ survey answers with blood uric acid levels, the researchers found seven foods associated with raised uric acid levels (beer, liquor, wine, potato, poultry, soft drinks, and meat) and eight foods associated with lowered uric acid levels (eggs, peanuts, cold cereals, skim milk, cheese, brown bread, margarine, and non-citrus fruit). Even so, when they calculated how big an influence each of these foods had on uric acid levels, they found that individually, the food items explained less than 1% of variation in uric acid levels in all participants.

The researchers then used four diet scores to see if general diet patterns affected variations in uric acid levels. Overall, the diet scores explained less than 0.3% of the variation in urate levels in the study participants.

Next, the researchers looked at 30 gene variations previously linked to blood uric acid levels in Europeans (since the study participants were all of European descent). They discovered that these common inherited genetic variants in the participants’ DNA could account for about 23.9% of the variation in uric acid levels. For instance, variants in the SLC2A9 gene, a gene linked to the transport of uric acid in the kidneys, were the most strongly associated in varying uric acid levels, explaining about 4% of the variation in uric acid levels. The researchers concluded that for their study participants, overall diet explained “much less variance in [uric acid] levels when compared with inherited genetic variants.”

The researchers acknowledged that the study had limitations. The data are specific to the European population without gout that they enrolled in their study. It is not clear whether their conclusions also apply to individuals with gout, since they were not studied.

This study was not designed to predict risk of developing gout or change treatment, and additional studies would be needed to determine whether individuals with these variants are more likely to develop gout. However, this work may impact people with gout and their healthcare providers by challenging “widely held community perceptions” that high uric acid levels are primarily caused by diet.

View Sources

(October 11, 2018) Young, K. Physician’s First Watch. NEJM Journal Watch: Diet may play less of a role in gout than previously thought. Available online at https://www.jwatch.org/fw114660/2018/10/11/diet-might-play-less-role-gout-previously-thought?query=pfw&jwd=000020042125&jspc=. Accessed on October 17, 2018.

(October 10, 2018) Major, T.J., et al. Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population-based cohorts. The BMJ. Available online at https://doi.org/10.1136/bmj.k3951. Accessed on October 18, 2018.

Arthritis Foundation. How Diet Affects Gout: What role does diet play in gout management? Available online at https://www.arthritis.org/about-arthritis/types/gout/articles/purine-foods-gout-attack.php. Accessed on October 17, 2018.

(October 11, 2018) Preidt, R. HealthDay. Genes, not diet, may be key to gout flare-ups. Available online at https://consumer.healthday.com/bone-and-joint-information-4/gout-news-338/genes-not-diet-may-be-key-to-gout-flare-ups-738458.html. Accessed on October 17, 2018.

(October 10, 2018) Major, T.J. thebmjopinion, author’s perspective. Tanya Major: Gout—is that genetic? Available online at https://blogs.bmj.com/bmj/2018/10/10/tanya-major-gout-is-that-genetic/. Accessed on October 19, 2018.

(October 16, 2018) National Institutes of Health, U.S. National Library of Medicine, Genetics Home Reference. Genes: SLC2A9 gene. Available online at https://ghr.nlm.nih.gov/gene/SLC2A9#conditions. Accessed on October 19, 2018.

(October 10, 2018) Kelly, J.C. Medscape Medical News: Genetics drive gout risk far more than diet. Available online at https://www.medscape.com/viewarticle/903245. Accessed on October 17, 2018.