Beschreibung:
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Salt-sensitivity of blood pressure (BP) is a risk factor for hypertension, cardiovascular disease and all-cause mortality. Although documented as an important BP endophenotype, the relationship between genetic loci implicated in BP and BP salt-sensitivity remains unexamined. We assessed the hypothesis that weighted genetic risk scores (GRS), based on SNPs identified in previous BP genome-wide association study meta-analyses, would predict BP salt-sensitivity among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. The GenSalt study was conducted among 1,906 participants from 633 Han Chinese families. Participants underwent a 7-day low sodium (51.3 mmol sodium/day), 7-day high sodium (307.8 mmol sodium/day), and 7-day high sodium plus potassium (60 mmol potassium/day) feeding study. BP was measured nine times at baseline and at the end of each intervention period using a random-zero sphygmomanometer. The relationships between systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) GRS and respective SBP, DBP and MAP responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, gender, field center, and baseline body mass index and BP. As expected, baseline SBP, DBP, and MAP significantly increased per quartile increase in GRS(p=5.6 х 10
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, p=1.3 х 10
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, and p=9.9 х 10
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). In contrast, increasing GRS quartile conferred smaller SBP, DBP, and MAP responses to the low sodium intervention (p=4.2 х 10
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, p=0.02, and p=7.3 х 10
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, respectively) and smaller SBP responses to the high sodium and potassium interventions (p=0.05 and p=0.03, respectively) (
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). Similar results were obtained when the data were analyzed per standard deviation increase in GRS. In summary, we identified an inverse relationship between BP GRS and BP salt-sensitivity. Further studies will be needed to elucidate the biological mechanisms contributing to this novel finding.
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