Associations of Genetic Variants in Uric Acid Transporter Genes With Salt Sensitivity, Longitudinal Blood Pressure Changes, and Incident Hypertension in Chinese Adults.
Chang M, Kong L, et al. • Journal of clinical hypertension (Greenwich, Conn.) • 2026
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.
Key Findings
Results
Multiple SNPs in ABCG2 were associated with diastolic blood pressure and mean arterial pressure responses to dietary sodium changes.
ABCG2 rs2054576 and rs4491984 were associated with DBP response to low-salt diet after multivariable adjustment and multiple-testing correction
ABCG2 rs12505410 was associated with DBP and MAP responses to dietary sodium
ABCG2 rs2054576 was also associated with longitudinal DBP and MAP change over 14 years of follow-up
Study was conducted in a family-based cohort of 514 Chinese adults from the Baoji Salt-Sensitivity Study
Results
SLC22A6 rs4149170 was associated with both salt sensitivity outcomes and long-term blood pressure changes.
SLC22A6 rs4149170 was associated with SBP and DBP responses to low-salt diet
The same variant was also associated with change in SBP, DBP, and MAP over the 14-year follow-up period
This dual association suggests SLC22A6 may play a sustained role in blood pressure regulation beyond acute sodium response
Results
ABCC4 variants were associated with salt sensitivity during both low-salt and high-salt dietary conditions, as well as long-term BP changes and incident hypertension.
ABCC4 rs1189466 and rs17189390 were associated with SBP, DBP, and MAP responses during low-salt diet
ABCC4 rs17189390 and rs9590211 were associated with SBP, DBP, and MAP responses during high-salt intake
ABCC4 rs1189466 was associated with longitudinal DBP and MAP change over 14 years
ABCC4 rs9590220 and rs7322318 were associated with change in SBP, DBP, and MAP longitudinally
ABCC4 rs7982809 and rs869951 were associated with incident hypertension over the 14-year follow-up
Results
SLC2A9 rs3733591 was associated with blood pressure responses during high-salt intake and with longitudinal systolic BP change.
SLC2A9 rs3733591 was associated with SBP and MAP responses during high-salt dietary intervention
The same SNP was associated with longitudinal SBP change over the 14-year follow-up
SLC2A9 encodes a key uric acid transporter (GLUT9) previously implicated in urate handling
Results
SLC22A11 rs3759053 was associated with blood pressure responses specifically during high-salt dietary conditions.
SLC22A11 rs3759053 was associated with SBP, DBP, and MAP responses during high-salt intake
No association was reported for this variant during low-salt conditions or longitudinal follow-up
This finding suggests a salt-load-specific mechanism for SLC22A11 in BP regulation
Results
SLC17A3 rs1165165 was associated with longitudinal systolic blood pressure change over 14 years.
SLC17A3 rs1165165 was associated with longitudinal SBP change across the 14-year prospective follow-up
No association was reported for this variant in the acute dietary sodium intervention phase
The association was identified after multivariable adjustment and multiple-testing correction
Results
SLC22A7 rs2270860 and SLC22A12 rs79226484 were associated with longitudinal diastolic BP and MAP changes.
SLC22A7 rs2270860 was associated with DBP and MAP change over the 14-year follow-up
SLC22A12 rs79226484 was also associated with DBP and MAP change longitudinally
SLC22A12 rs7932775 was associated with DBP and MAP responses during the low-salt dietary intervention
Methods
The study used a controlled dietary sodium intervention followed by 14 years of prospective follow-up in a family-based Chinese cohort.
514 Chinese adults from the Baoji Salt-Sensitivity Study completed the controlled dietary sodium intervention
The cohort is family-based and located in Baoji, China
Participants were followed prospectively for 14 years after the sodium intervention
Outcomes included salt sensitivity (acute BP response to low- and high-salt diet), longitudinal BP changes, and incident hypertension
Analyses included multivariable adjustment and multiple-testing correction
Methods
Eight urate transporter genes containing common SNPs were examined for associations with blood pressure phenotypes.
Genes studied included SLC2A9, ABCG2, SLC17A3, SLC22A7, SLC22A6, SLC22A11, SLC22A12, and ABCC4
These genes encode renal and extrarenal urate transporters involved in urate handling
Common single-nucleotide polymorphisms (SNPs) within these genes were the primary exposure variables
The study examined associations with salt sensitivity, longitudinal BP changes, and incident hypertension as outcomes
What This Means
This research suggests that common genetic differences in genes responsible for transporting uric acid in the body are linked to how a person's blood pressure responds to salt, how blood pressure changes over many years, and the risk of developing high blood pressure. The study followed 514 Chinese adults from the Baoji region for 14 years, beginning with a controlled experiment where participants consumed low-salt and high-salt diets. Researchers found that variants in several uric acid transporter genes — including ABCG2, ABCC4, SLC22A6, SLC2A9, and others — were associated with blood pressure responses to these dietary changes, as well as with long-term blood pressure trends and new cases of hypertension over the follow-up period.
The findings are notable because they connect two biological systems not always considered together: uric acid handling by the kidneys and blood pressure regulation. Uric acid is a waste product filtered by the kidneys, and the genes studied control how it is transported in and out of cells. This research suggests that the same molecular machinery involved in managing uric acid may also influence how the body handles salt and regulates blood pressure over time. Some gene variants, particularly in ABCC4, appeared relevant to both acute salt responses and long-term hypertension risk.
This research suggests that genetic screening for urate transporter variants could potentially help identify individuals at higher risk of salt-sensitive hypertension or long-term blood pressure progression. It also points to uric acid transport pathways as possible targets for understanding or treating high blood pressure, though further research in larger and more diverse populations would be needed to confirm these findings and assess their clinical relevance.
Chang M, Kong L, Zhang Z, Yao S, Wang X, Li H, et al.. (2026). Associations of Genetic Variants in Uric Acid Transporter Genes With Salt Sensitivity, Longitudinal Blood Pressure Changes, and Incident Hypertension in Chinese Adults.. Journal of clinical hypertension (Greenwich, Conn.). https://doi.org/10.1111/jch.70361