OP0202 DOES EXCESS WEIGHT AFFECT GOUT RISK DIFFERENTLY AMONG GENETICALLY PREDISPOSED INDIVIDUALS? – SEX-SPECIFIC PROSPECTIVE COHORT FINDINGS OVER >26 YEARS

Abstract

Background:Global burden of gout has increased substantially, particularly among women.1,2 Addressing obesity, a major modifiable risk factor for gout, may alleviate this burden; however, there is also a significant genetic contribution to gout risk according to the genome-wide association studies (GWAS).3,4 Genetic predisposition may modify the excess weight effect on gout risk.Objectives:To investigate the potential role of genetic predisposition on the association between excess weight (i.e., BMI ≥ 25 kg/m2) and gout risk in two US prospective longitudinal cohorts over >26 years, stratified by sex.Methods:We examined the association between excess weight and risk of incident gout meeting the ACR survey criteria,5 according to genetic risk, in 18,512 women from the Nurses’ Health Study (NHS) over 32 years, and 10,917 men from Health Professionals Follow-Up Study (HPFS) over 26 years. We derived a genetic risk score (GRS) using 114 serum urate single nucleotide polymorphisms from the latest GWAS.3 We also calculated the population attributable risk (PAR) for excess weight according to GRS stratum.Results:We ascertained 530 incident gout cases in NHS and 983 in HPFS. While the relative risks (RRs) due to excess weight (overweight or obesity) appeared larger among women above the mean than below the mean, the RRs among men appeared similar according to genetic predisposition (Table 1). The RRs among women for excess weight compared to normal were 1.66 (95% CI, 1.17 to 2.37) and 2.55 (1.95 to 3.34) below and above the mean GRS, respectively (P for multiplicative interaction = 0.06), whereas corresponding RRs among men were 1.68 (95% CI, 1.31 to 2.16) and 1.76 (1.47 to 2.10) (P for multiplicative interaction = 0.8). The risk differences (RD) among women for excess weight were 0.69 and 2.38 with GRS below and above the mean, respectively, resulting in the relative excess risk due to interaction (RERI) of 1.69 (95% CI, 1.03 to 2.35, P for additive interaction = 5.4x10-7); for men, the corresponding RDs were 0.70 and 1.46, with RERI = 0.76 (0.26, 1.25; P for additive interaction = 2.6x10-3). Excess weight accounted for a larger proportion of incident gout cases among women with GRS above the mean (PAR, 48.5% [95% CI, 38.8 to 55.9]) compared to those with GRS below the mean (PAR, 29.0% [95% CI, 10.5 to 42.1]), whereas the PARs among men were similar (31.6% vs 29.7%, respectively).Table 1.Relative Risk of Gout by Body Mass Index, Stratified by Mean Genetic ScoreHPFS (men)Below MeanAbove MeanBMIOverall<2525-30>30Overall<2525-30>30No. Cases3338817273650172349129Person-Years10405543314492531148898634419944609610544Age-Adjusted RR-1.0 (ref)1.71 (1.32, 2.22)3.00 (2.18, 4.12)-1.0 (ref)1.80 (1.50, 2.16)2.87 (2.27, 3.62)MV Adjusted* RR-1.0 (ref)1.53 (1.18, 1.99)2.31 (1.66, 2.21)-1.0 (ref)1.63 (1.35, 1.96)2.38 (1.87, 3.03)NHS (women)Below MeanAbove MeanBMIOverall<2525-30>30Overall<2525-30>30No. Cases17347408635772120165Person-Years24439212384976414441292392591202297612342907Age-Adjusted RR-1.0 (ref)1.23 (0.81, 1.88)4.46 (3.10, 6.41)-1.0 (ref)2.41 (1.79, 3.23)5.68 (4.82, 7.52)MV Adjusted* RR-1.0 (ref)1.00 (0.65, 1.53)2.84 (1.92, 4.20)-1.0 (ref)1.97 (1.46, 2.65)3.61 (2.68, 4.87)*Adjusted for age (continuous), menopause, use of hormone therapy (never, past or current), history of hypertension, and systolic and diastolic blood pressure, alcohol, total energy intake and intake of meat, seafood and dairy foods (all continuous).Conclusion:These large scale longitudinal prospective cohorts suggest maintaining healthy weight is an important gout prevention strategy, regardless of underlying genetic risk. In genetically predisposed individuals, addressing excess weight may prevent a large proportion of gout cases, especially among women.