High levels of serum uric acid are associated with hypertension in observational studies. The aim of this study was to investigate the association of uric acid gene variants with blood pressure. We studied 5791 participants aged ≥55 years from the Rotterdam Study. Thirty gene variants identified for serum uric acid level were used to compile genetic risk score (GRS). We used linear regression models to investigate the association of the uric acid GRS with systolic and diastolic blood pressure in the whole study population and separately in participants with and without comorbidities and medication use. In the age- and sex-adjusted model, each SD increase in uric acid GRS was associated with 0.75 mm Hg lower systolic blood pressure (95% confidence interval, -1.31 to -0.19) and 0.42 mm Hg lower diastolic blood pressure (95% confidence interval, -0.72 to -0.13). The association did not attenuate after further adjustment for antihypertensive medication use and conventional cardiovascular risk factors. In subgroup analysis, the association of uric acid GRS with systolic blood pressure was significantly stronger in participants (n=885) on diuretic treatment (P for interaction, 0.007). In conclusion, we found that higher uric acid GRS is associated with lower systolic and diastolic blood pressure. Diuretics treatment may modify the association of uric acid genetic risk score and systolic blood pressure. Our study suggests that genome wide association study's findings can be associated with an intermediate factor or have a pleiotropic role and, therefore, should be applied for Mendelian Randomization with caution.

Additional Metadata
Keywords Blood pressure, Diuretics, Genetic pleiotropy, Uric acid
Persistent URL dx.doi.org/10.1161/HYPERTENSIONAHA.114.03757, hdl.handle.net/1765/89725
Journal Hypertension
Citation
Sedaghat, S, Pazoki, R, Uitterlinden, A.G, Hofman, A, Stricker, B.H.Ch, Ikram, M.A, … Dehghan, A. (2014). Association of uric acid genetic risk score with blood pressure: The rotterdam study. Hypertension, 64(5), 1061–1066. doi:10.1161/HYPERTENSIONAHA.114.03757