Interaction between obesity and genetic predisposition add to gout risk, particularly among women, according to research results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.
The current study included 18,247 women and 10,899 men from the Nurses’ Health Study and Health Professionals Follow-Up Study, respectively. Clinical risk factors for gout were similar among the 2 cohorts, regardless of genetic risk. To quantify genetic predisposition, a genetic risk score (GRS) was used with 114 serum urate single-nucleotide polymorphisms, as described in the latest genome-wide association studies; a higher risk for hyperuricemia was indicated by higher GRS scores. Men and women were assessed separately for interactions between gene and body mass index (BMI), and a population attributable risk (PAR) for excess weight was noted by the GRS stratum.
Study researchers observed incident gout in 1361 women and 1704 men. Within the BMI categories of less than 25, 25 to 30, and greater than 30, women with GRS below the mean had multivariable relative risks of 1.0, 1.24 (0.98-1.57), and 2.60 (2.09-3.24), respectively; those in the GRS above the mean stratum had relative risks of 1.55 (1.25-1.91), 2.74 (2.2-3.35), and 4.65 (3.80-5.68), respectively. For GRS above and below the mean, a significant additive interaction with rate difference was observed between BMI greater than 30 (3.94/1000 person-years) and within 25 (1.70/1000 person-years), respectively, which resulted in a relative excess risk due to interaction of 1.48 (95% CI, 0.82-2.13; P <.01).
Study researchers observed a similar trend for men. The relative risk for excess weight was larger for those in the GRS above the mean stratum. The respective rate differences for GRS above and below the mean were 7.57/1000 person-years and 5.01/1000 person-years (relative excess risk due to interaction=0.58 (95% CI, -0.08 to 1.23; P =.08). Excess weight among women was associated with a greater proportion of gout cases in those with GRS above-the-mean stratum (PAR, 48.5%; 95% CI, 38.8-55.9) vs GRS below-the-mean (PAR, 29%; 95% CI, 10.5-42.1). Men showed similar PARS (31.6% and 29.7% for GRS above and below the mean, respectively).
Researchers concluded that there exists a “significant interaction between obesity and genetic predisposition among women, and a trend towards this in men.” They added, “Maintaining a healthy weight is an important gout prevention strategy, particularly among those with underlying genetic risk.”
Yokose C, McCormick N, Lu N, Joshi A, Choi HK. Does obesity affect gout risk differently among genetically predisposed individuals?: Sex-specific prospective cohort study findings over >32 years. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 672.