Association of Uric Acid Genetic Risk Score With Blood Pressure

Abstract

Abstract-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. Measurement of Serum Uric Acid and Blood PressureValues of serum uric acid were obtained from nonfasting blood samples, which were centrifuged for 10 minutes at 3000 rpm and subsequently stored at −20°C for 1 week. Uric acid activity was ascertained with Kone Diagnostica reagent kit and Kone autoanalyzer. To check the calibration, for every 10 samples, 3 control samples were included. In each run (100 samples), if the average values of the control samples were not within 2.5% of the true value, the run was repeated. Calibration was also done on day-by-day variation, which had to be within 5%. 10After a resting period of 5 minutes, blood pressure was measured twice in a single visit using a random-zero sphygmomanometer (cuff size of 32×17) on the right arm of participants in sitting position. The average of 2 measurements, separated by a count of the pulse rate, was used in the analyses. 11 CovariatesBody mass index was calculated by dividing weight in kilograms by height in meters squared. Information on alcohol consumption was acquired from the questionnaires. Participants were asked for the average daily consumption of alcohol. Medication use information was based on home interview. Diabetes mellitus was defined as the use of blood glucose-lowering medications or a random nonfasting glucose >11.1 mmol/L.12 Coronary heart disease was considered as having experienced myocardial infarction or undergone coronary revascularization procedures.13 Serum creatinine was determined using nonkinetic alkaline picrate (Jaffé) method. Estimated glomerular filtration rate was calculated using the simplified Modification of Di...

Uric acid and cardiovascular risk: What genes can say

“…The association did not attenuate after further adjustment for antihypertensive medication use and conventional cardiovascular risk factors. Noteworthy, in a subgroup analysis the association of UA GRS with systolic blood pressure was significantly stronger in participants (n = 885) on diuretic treatment ( P = .007) . In conclusion, higher UA GRS was associated with lower systolic and diastolic blood pressure, while diuretics treatment may modify the association of UA genetic risk score with systolic blood pressure .…”

“…Noteworthy, in a subgroup analysis the association of UA GRS with systolic blood pressure was significantly stronger in participants (n = 885) on diuretic treatment ( P = .007) . In conclusion, higher UA GRS was associated with lower systolic and diastolic blood pressure, while diuretics treatment may modify the association of UA genetic risk score with systolic blood pressure . The discrepancy between these findings and other studies could be explained in different ways .…”

“…What is more, UA might be causally involved in long‐term adverse cardiovascular outcomes by mechanisms that are independent of atherosclerosis and that would be an explanation of the lack of evidence of association of UA levels with classic atherothrombotic risk factors and markers, including diabetes mellitus, subclinical atherosclerosis and triglyceride levels . It has consistently been reported that UA concentration is associated with left ventricular hypertrophy, a major risk factor for sudden cardiac death and incident ventricular arrhythmia .…”

Serum uric acid and the risk of cardiovascular and renal disease

“…In a study by Hughes et al [17], a uric acid genetic risk score was associated with improved renal function. However, in a further genetic risk score study, Sedaghat et al [18] found 30 gene variants that were associated with increased serum uric acid but with lower blood pressure. In that study, the results were sensitive to diuretic therapy, and there was no relationship between a SLC2A9 SNP and BP in patients not treated with diuretics.…”

Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options

“…However, many studies [17, 66–72], even when largely powered, reached opposite conclusions, despite two of them showing an association of GRSs with gout [66, 71] (Table 3). The Rotterdam cohort showed a negative association between hyperuricaemic GRS and blood pressure, even stronger in patients receiving diuretics [69]. The use of several gene variants in the GRS increased the possibility that some of the included genes (or genes in linkage disequilibrium with them, which are not independently distributed during meiosis) had other effects than their soluble uric acid (SUA)-modulating property, a phenomenon called pleiotropy, which could be an important confounder.…”