rs10930597 (JPT1P1-CBY1P1): Blood Pressure Salt Response

Key takeaways

• Identified in a controlled dietary intervention study where participants cycled through low-sodium, high-sodium, and potassium-supplementation diets
• Carriers of more risk alleles across identified loci had up to 1.84 times the odds of developing hypertension over 7.5 years
• Also linked to blood pressure reactivity during the cold pressor test, a measure of sympathetic nervous system response
• Evidence is from Han Chinese participants only; generalizability to other ancestries is not yet established

What the research says This variant was identified in a genome-wide association study (GWAS) of blood pressure (BP) responses to three controlled dietary interventions - low-sodium, high-sodium, and high-sodium plus potassium supplementation - and to the cold pressor test (CPT), a procedure in which a hand is briefly immersed in ice water to measure sympathetic nervous system-driven BP reactivity, conducted in 1,881 Han Chinese individuals with de novo replication in 698 additional Han Chinese participants. Across the novel loci identified in the study, individuals carrying the most risk alleles had odds of developing hypertension 1.84 times higher (95% CI 1.29-2.62) than those carrying the fewest over a 7.5-year follow-up, with a significant dose-response trend (P=0.0003). The authors note that effect sizes on BP response phenotypes were larger than those typically observed in GWAS of usual BP levels.

Reported associations

• Blood pressure response to low-sodium diet: Identified in a 7-day controlled dietary intervention providing 51.3 mmol sodium per day in Han Chinese participants
• Blood pressure response to high-sodium diet: Identified in a 7-day controlled high-sodium dietary intervention (307.8 mmol sodium/day)
• Blood pressure response to potassium supplementation: Identified in a 7-day high-sodium plus potassium supplementation (60 mmol/day) intervention arm
• Blood pressure response to cold pressor test: Associated with sympathetic-mediated BP reactivity during cold-water hand immersion
• Incident hypertension: Risk allele burden across identified loci predicted hypertension development over 7.5-year follow-up; odds ratio 1.84 (95% CI 1.29-2.62) for the highest versus lowest risk-allele quartile

Evidence quality The discovery cohort comprised 1,881 Han Chinese participants and replication was conducted de novo in 698 additional Han Chinese individuals from the same geographic region; study compliance was verified through timed urinary sodium and potassium excretion measurements. Genome-wide-level p-values were reported for the eight identified loci, ranging from 3.57×10^-8 to 7.01×10^-¹³. Effect sizes on BP response phenotypes are described by the authors as notably larger than those from prior GWAS of usual BP levels. Key limitations include restriction to a single ethnic group (Han Chinese from rural northern China) and absence of replication in non-Han Chinese populations in the provided source material; evidence should be considered preliminary pending broader multi-ancestry validation.

Lifestyle considerations

• Dietary sodium (nutrition, mixed, low): Blood pressure responses to both restricted and high sodium intake showed inter-individual genetic variation in a controlled dietary intervention study, suggesting this locus may influence sodium sensitivity.
• Dietary potassium (nutrition, mixed, low): Potassium supplementation was a distinct intervention arm in the study, with blood pressure responses demonstrating genetic variability across participants.