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Gene-diet and gene-weight interactions associated with the risk of gout

Presented by
Dr Chio Yokose, Massachusetts General Hospital, USA
EULAR 2021
Adhering to the healthy Dietary Approaches to Stop Hypertension (DASH) diet decreased the risk of gout in women. This effect was more pronounced in genetically predisposed individuals. Also, a large proportion of incident gout cases can be accounted to excess weight in addition to genetic predisposition. These were the main conclusions of 2 prospective cohort studies investigating gene-environment interaction effects in gout [1-2]. The authors concluded that public interventions targeting diet and excess weight could have a big impact on the growing number of incident gout cases worldwide.

Although gout predominantly occurs in men, a Global Burden of Disease Study analysis revealed a rise in gout burden worldwide, especially among women [3]. Therefore, studying this condition in women has become increasingly important.

Dr Chio Yokose (Massachusetts General Hospital, USA) presented the results of 2 separate analyses from 2 prospective general health cohort studies: Nurses’ Health Study (NHS; n=18,247 women; 1984–2018) and the Health Professionals Follow-Up Study (HPFS; n=10,899 men; 1986–2018).

In the NHS, 530 incident gout cases were discovered; 983 cases were observed in the HPFS. Genetic risk scores (GRS) were calculated based on 114 urate SNPs from European ancestry meta-analyses. Biennial health questionnaires including incident gout, BMI, and data on exposure to the DASH diet (considered healthy) and western diet (considered unhealthy) were collected. The first analysis assessed the potential interaction effect between genetic predisposition and diet on incident gout in US women, based on data from the NHS [1]. Cox proportional hazards model was used to analyse the association between genetics, diet, and the risk of incident gout. Based on GRS scores, participants were divided into 2 groups: those with an elevated genetic risk of gout (GRS above the mean) and those with a low genetic risk of gout (GRS below the mean). Diet adherence was categorised in quintiles. Three BMI groups were computed: normal weight (BMI <25), overweight (BMI 25–29.9), and obese (BMI ≥30). The model was adjusted for known risk factors of gout, such as age, BMI, red meat consumption, and the use of diuretics.

The risk of gout increased in women who adhered less to the DASH diet, especially in genetically predisposed women. The relative risk of women with high GRS increased from 1.76 (best adherence to DASH diet) to 2.79 (worst adherence to DASH diet; see Figure). In women with low GRS, the relative risk increased from 1 (best adherence to DASH diet) to 1.43 (worst adherence to DASH diet). Subsequent interaction analysis trended towards significance, with a relative excess risk due to interaction (RERI) of 0.57 (P=0.06). No genetics-diet interaction effect on incident gout was observed for the western diet (RERI 0.20;  P=0.52).

Figure: Joint impact of DASH diet and GRS on the relative risk of incident gout in women [1]

GRS, genetic risk score; DASH, Dietary Approaches to Stop Hypertension; Q, quintile of diet adherence: Q1 is lowest adherence, Q5 is highest adherence.

The second analysis was based on both cohorts and examined to what extent excess weight and genetic predisposition for gout interact on the risk of incident gout. Although excess weight is an established risk factor for gout, weight-gene interaction effects have not yet been analysed in prior gout studies.

Results demonstrated that excessive weight in men was related to an increased risk of incident gout. Analysis of the GRS showed that this effect was amplified in genetically predisposed men. Relative excess risk for excess weight (overweight or obese) compared with normal weight trended towards significance (P=0.08). The investigated interaction effect was more profound among women with excess weight. Additive interaction analysis confirmed this; incident gout was higher in overweight and obese women with a high genetic risk compared with overweight and obese women with a low genetic risk (RERI 1.69; P<0.01).

Dr Yokose argued that the results of these 2 prospective cohort studies suggest that dietary interventions and lifestyle interventions targeting weight can significantly reduce the number of gout cases. Women who have a genetic predisposition for gout could particularly benefit from this. However, further work is needed before a GRS could be applied to gout prediction.

  1. Yokose C, et al. Gene-Diet Interaction on the Risk of Incident Gout Among Women: Prospective Cohort Study over 34 Years. OP0203, EULAR 2021 Virtual Congress, 2–5 June.
  2. Yokose C, et al. Does Excess Weight Affect Gout Risk Differently Among Genetically Predisposed Individuals? Sex-Specific Prospective Cohort Findings over > 32 Years. OP0202, EULAR 2021 Virtual Congress, 2–5 June.
  3. Safiri S, et al. Arthritis Rheumatol. 2020; 72(11):1916-27.


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