The AG/GG group displayed a rebound in SBP from 8 weeks, differing from the consistent decrease in the AA group (<i>P</i>=0.004 for difference in trajectories).<h4>Conclusions</h4>Our results confirm a plausible interaction between UMOD and NKCC2 and suggest a potential role for genotype-guided use of loop diuretics in hypertension management.<h4>Registration</h4>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354897. This evidence concerns the gene SLC12A1 and hypertensive disorder.