Genetic Risk, Adherence to a Healthy Lifestyle, and Hyperuricemia: The TCLSIH Cohort Study.

ABSTRACT

BACKGROUND: Genetic factors have been associated with hyperuricemia in large studies, but the extent to which this can be offset by a healthy lifestyle is unknown. This study aimed to examine whether healthy lifestyle could reduce hyperuricemia risk among individuals with different genetic profiles. METHODS: We defined a lifestyle score using body mass index, smoking, alcohol consumption, physical activities, and diets in 2796 unrelated individuals from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study. Polygenic risk scores (PRS) were constructed based on uric acid loci. Associations of combined lifestyle factors and genetic risk and incident hyperuricemia were estimated using Cox proportional hazard regression. RESULTS: Of 2796 individuals, 747 participants (26.7%) developed hyperuricemia. Genetic risk and lifestyle were predictors of incident events, and they showed an interaction for the outcome. Compared with high PRS, low PRS reduced risk of incident hyperuricemia by 40%, and compared with unhealthy lifestyle, healthy lifestyle reduced risk of incident hyperuricemia by 41%. Compared with unhealthy lifestyle and high genetic risk, adherence to healthy lifestyle was associated with a 68% (95% confidence interval, 44%-81%) lower risk of hyperuricemia among those at a low genetic risk. CONCLUSIONS: In this prospective cohort study, we observed an interaction between genetics and lifestyle and the risk of hyperuricemia. The public health implication is that a healthy lifestyle is important for hyperuricemia prevention, especially for individuals with high genetic risk scores.