Excess adiposity and genetic predisposition are strongly associated with a higher risk of gout, particularly in women.

INTRODUCTION
Gout is a very common condition, affecting up to 2–4% of adults in developed countries. The symptoms tend to flare every so often, developing over a few hours and causing severe pain in the joints. It is caused by deposits of crystals of a substance called uric acid (urate) in the joints, which leads to inflammation. Two known risk factors for gout are a person’s genetics, and carrying too much body fat (excess adiposity). However, research in this area has focused on men. Gout is often thought of as a male disease, but it also affects women – mainly after menopause. Some risk factors appear to be stronger in men than women and vice-versa. New information suggests the number of women with gout and its severity is rising faster than in men.

WHAT DID THE AUTHORS HOPE TO FIND?
The authors wanted to evaluate the impact of having excess adiposity and genetic predisposition – both alone and in combination – on the risk of developing gout in women. They then intended to compare this to the effects in men.

WHO WAS STUDIED?
The study looked at over 18,000 women. Everyone was taking part in one of three long-term studies of healthcare professionals from across the USA. Nobody had gout at the start. Some people took part in the study for more than 32 years.

HOW WAS THE STUDY CONDUCTED?
This was a prospective observational study. This means everyone taking part was observed over a period of time and measurements taken, but there was no study intervention or medicine being tested.
Everyone taking part had a blood test to check whether they had one or more of the genes that predispose people to developing gout. Using this information, each person was given a genetic risk score. Everyone also filled in questionnaires when they entered the study, and again every 2–4 years after that. The questionnaires collected information on their medical history, new diagnoses, medications, diet, and other lifestyle factors. This included updating their weight so that the authors could calculate their body mass index (BMI) and work out how much excess adiposity they had.

The authors analysed the information from the questionnaires and the results of the genetic profiling and categorised each person by their degree of adiposity, and their genetic risk score. They then compared the impact of adiposity and genetic predisposition on the risk of developing gout. Statistics were used to account for other factors that affect the risk of gout, such as eating meat and seafood, having high blood pressure, taking diuretic medications, or taking postmenopausal hormone therapy. The authors analysed each group separately, and compared the findings between women and men.

WHAT WERE THE MAIN FINDINGS OF THE STUDY?
The main finding was that in both women and men, higher adiposity and higher genetic risk were associated with an increased risk of gout. For example, compared to those with BMI in the normal range, obese women were 3-times more likely to develop gout, and men were 2.2-times more likely. Having an above-average genetic risk score was associated with 60–80% increased risk of developing gout.

However, the risk for the two exposures combined was greater than the sum of its parts. This suggests
that excess adiposity worsens a person’s genetic predisposition to developing gout. For example, compared to women with BMI in the normal range and below-average genetic risk, obesity alone increased the risk of female gout by 2.6-times, and above-average genetic risk alone increased the risk by 1.9-times. But having both obesity and above-average genetic risk increased the risk of gout by 4.5-times. Interestingly, this interaction was stronger in women than in men.

ARE THESE FINDINGS NEW?
Yes, this was the first study looking at these interactions for the risk of newly diagnosed gout.

WHAT ARE THE LIMITATIONS OF THE STUDY?
Like any observational study, there is always the possibility of confounding because people are not randomly assigned to the exposure, so it is possible that there is something else affecting the gout risk in people with higher adiposity. This is less of a concern for genetics, because your genetic profile is fixed.

WHAT DO THE AUTHORS PLAN ON DOING WITH THIS INFORMATION?
The authors think it would be good to investigate the mechanisms behind these findings, especially the sex-specific effects, which may be driven by sex hormones. In addition, everyone taking part had European ancestry. It would be good to investigate these interactions in other groups, where some additional gout risk genes (different from those in European ancestry populations) have been identified.

WHAT DOES THIS MEAN FOR ME?
If you have gout – or might be at risk of developing it – you should try to maintain a healthy body weight. Your risk of gout is affected by both your genetics and your weight. It is not possible to change your genetics, but you can manage your excess adiposity. Though not always easy, efforts to reduce body weight could play a major role in preventing gout and its effects on your heart and other organs.

If you have any concerns about your disease or its treatment, you should speak to your doctor.

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Date prepared: March 2022
Summary based on research article published on: 2 December 2021
From: McCormick N, et al. Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over >32 years. Ann Rheum Dis 2022;81:556–63. doi:10.1136/annrheumdis-2021-221635

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