Healthy Lifestyle May Attenuate the Genetic Risk of Gout

Persistent hyperuricemia (elevated levels of uric acid in the blood) causes deposition of monosodium urate crystals within joints, leading to a common form of inflammatory arthritis called gout. Along with frequent flares of pain and swelling in the joints, gout is often associated with comorbidities such as cardiovascular disease, hypertension, chronic kidney disease, and more. While urate-lowering therapy can provide individuals with gout a means of controlling gout flares, clinical management of gout remains substandard. Identifying individuals who are at risk of developing gout may aid in prevention and subsequent complications associated with gout.

Prior studies have been successful in identifying genetic variants that are associated with hyperuricemia and gout, including SLC2A9, ABCG2, GCKR, and SLC22A11. Additionally, it has been well documented in other studies that lifestyle factors, including alcohol consumption, smoking, diet, physical activity, and body mass index, share an association with gout risk. However, whether healthy lifestyle factors can alleviate the genetic risk of gout remains unclear.

Researchers “aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors” in a study published in BMC Medicine.

The population-based cohort study identified 416,481 gout-free participants. Polygenic risk for gout was assessed and categorized as low, middle, and high. Researchers defined healthy lifestyle factors as including no/moderate alcohol consumption, no smoking, physical activity, and a healthy diet. Based on these criteria, participants were categorized into groups according to their number of healthy lifestyle factors: unfavorable, intermediate, and favorable.

Study participants were followed for a median 12.1 years, and 6206 developed gout by the final follow-up. Compared to the gout-free participants, participants who developed gout were more likely to be older, male, excessive alcohol drinkers, smokers, physically inactive, or to have an unhealthy diet.

The researchers conducted a joint effect analysis of genetic predisposition and lifestyle factors to determine an association. Participants with middle and high genetic predisposition plus unfavorable lifestyle profiles were significantly more likely to develop gout when compared with participants with low genetic predisposition and a favorable lifestyle. Further analyses showed that the risk of developing gout was significantly lessened regardless of genetic risk when related to a favorable lifestyle.

“There was a significant additive interaction between unfavorable lifestyle and high genetic risk of gout,” researchers wrote, “Our findings highlight the importance of maintaining a healthy lifestyle for the prevention of gout in people with a genetic predisposition.”