Associations of Genetic Variants in Uric Acid Transporter Genes With Salt Sensitivity, Longitudinal Blood Pressure Changes, and Incident Hypertension in Chinese Adults

Uric acid transporters mediate renal and extrarenal urate handling and may contribute to blood pressure (BP) regulation. This study examined the associations of common single-nucleotide polymorphisms (SNPs) in key urate transporter genes (SLC2A9, ABCG2, SLC17A3, SLC22A7, SLC22A6, SLC22A11, SLC22A12, and ABCC4) with salt sensitivity, longitudinal BP changes, and incident hypertension. Data were derived from the Baoji Salt-Sensitivity Study, a family-based cohort in which 514 Chinese adults completed a controlled dietary sodium intervention and were followed prospectively for 14 years. After multivariable adjustment and multiple-testing correction, ABCG2 rs2054576 and rs4491984 were associated with DBP response to low-salt diet; SLC22A6 rs4149170 with SBP and DBP responses; ABCG2 rs12505410 and SLC22A12 rs7932775 with DBP and MAP responses; and ABCC4 rs1189466 and rs17189390 with SBP, DBP, and MAP responses. During high-salt intake, SLC2A9 rs3733591 was associated with SBP and MAP responses; and SLC22A11 rs3759053, ABCC4 rs17189390 and rs9590211 were associated with SBP, DBP, and MAP responses. Over 14 years of follow-up, SLC2A9 rs3733591 and SLC17A3 rs1165165 were associated with longitudinal systolic BP (SBP) change; ABCG2 rs2054576, SLC22A7 rs2270860, SLC22A12 rs79226484, and ABCC4 rs1189466 were associated with diastolic BP (DBP) and MAP change; and SLC22A6 rs4149170 and ABCC4 rs9590220 and rs7322318 were associated with change in SBP, DBP and MAP. Additionally, ABCC4 rs7982809 and rs869951 were associated with incident hypertension over the 14-year follow-up. These findings suggest that genetic variation in urate transporters may contribute to salt sensitivity, long-term BP progression, and hypertension risk, supporting a possible role for urate-transport pathways in BP regulation.