Disclosures: The study was supported by the NIH. McCormick reports no other relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
December 15, 2021
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Obesity plus genetic predisposition exacerbates risk for gout in women

Disclosures: The study was supported by the NIH. McCormick reports no other relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Although excess adiposity and genetic predisposition are individually strongly linked to greater gout risk, both combined result in a higher risk than the sum of each, especially in women, according to data.

“Gout has often been considered a disease of men, but many women do develop gout, predominantly after menopause, and they have a higher frequency of obesity and associated cardiometabolic comorbidities than do men with gout,” Natalie McCormick, PhD, of Massachusetts General Hospital, in Boston, told Healio Rheumatology.

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Although excess adiposity and genetic predisposition are individually strongly linked to greater gout risk, both combined result in a higher risk than the sum of each, especially in women, according to data derived from McCormick N, et al. Ann Rheum Dis. 2021;doi:10.1136/annrheumdis-2021-221635.

“In fact, latest data from the Global Burden of Disease study suggests the prevalence and disability burden of female gout is rising disproportionately to male gout,” she added. “To help dampen this burden, we need to better understand the risk factors and potential mechanisms for development of female gout, and how these differ from male gout.”

To examine the link between adiposity combined with genetic predisposition and the risk for gout in women, compared with men, McCormick and colleagues prospectively analyzed data from the Nurses’ Health Study (NHS), as well as from a younger cohort from NHS II. The researchers studied potential gene-BMI interactions in 18,244 women from the NHS, which enrolled U.S. registered nurses who were aged 30 to 55 years at baseline in 1976, and compared them with 10,888 men from the Health Professionals Follow-Up Study, a prospective cohort of U.S. male clinicians who were aged 40 to 75 years in 1986.

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Natalie McCormick

The researchers then replicated their analysis in 8,246 women from the NHS II, a prospective cohort study of female registered nurses in the United States aged 25 to 42 years at enrollment in 1989. All individuals included in the analysis demonstrated no history of gout at baseline. The researchers determined genetic risk scores for hyperuricemia based on 114 common urate-associated single nucleotide polymorphisms.

According to the researchers, who published their findings in the Annals of the Rheumatic Diseases, multivariable RR for gout in women was 1.49 (95% CI, 1.42-1.56) per 5 kg/m2 increment of BMI, and 1.43 (95% CI, 1.35-1.52) per standard deviation increment in the genetic risk score. For the combined association of BMI and genetic risk score, RR was 2.18 (95% CI, 2.03-2.36), more than the sum of each individual factor, suggesting significant interaction on an additive scale (P < .001), the researchers wrote.

The attributable proportions of joint impact for gout in women were 42% (37% to 46%) for adiposity, 37% (32% to 42%) for genetic predisposition and 22% (16% to 28%) for their interaction. Meanwhile, the additive interaction among men was smaller, albeit still significant, and the attributable proportion of joint impact was 14% (6% to 22%).

“These findings reiterate the importance of keeping a healthy weight to help prevent the development of female gout, among other cardiometabolic diseases,” McCormick said. “Excess weight was a risk factor among all women, but for women who were genetically predisposed to developing gout, excess weight served to exacerbate this even more.”