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  1. Tan JW, Gupta T, Manosroi W, Yao TM, Hopkins PN, Williams JS, et al.
    JCI Insight, 2017 12 07;2(23).
    PMID: 29212952 DOI: 10.1172/jci.insight.95992
    Compared with persons of European descent (ED), persons of African descent (AD) have lower aldosterone (ALDO) levels, with the assumption being that the increased cardiovascular disease (CVD) risk associated with AD is not related to ALDO. However, the appropriateness of the ALDO levels for the volume status in AD is unclear. We hypothesized that, even though ALDO levels are lower in AD, they are inappropriately increased, and therefore, ALDO could mediate the increased CVD in AD. To test this hypothesis, we analyzed data from HyperPATH - 1,788 individuals from the total cohort and 765 restricted to ED-to-AD in a 2:1 match and genotyped for the endothelin-1 gene (EDN1). Linear regression analyses with adjustments were performed. In the total and restricted cohorts, PRA, ALDO, and urinary potassium levels were significantly lower in AD. However, in the AD group, greater ALDO dysregulation was present as evidenced by higher ALDO/plasma renin activity (PRA) ratios (ARR) and sodium-modulated ALDO suppression-to-stimulation indices. Furthermore, EDN1 minor allele carriers had significantly greater ARRs than noncarriers but only in the AD group. ARR levels were modulated by a significant interaction between EDN1 and AD. Thus, EDN1 variants may identify particularly susceptible ADs who will be responsive to treatment targeting ALDO-dependent pathways (e.g., mineralocorticoid-receptor antagonists).
  2. Gupta T, Connors M, Tan JW, Manosroi W, Ahmed N, Ting PY, et al.
    Am J Hypertens, 2017 Dec 08;31(1):124-131.
    PMID: 28985281 DOI: 10.1093/ajh/hpx146
    BACKGROUND: Understanding the interactions between genetics, sodium (Na+) intake, and blood pressure (BP) will help overcome the lack of individual specificity in our current treatment of hypertension. This study had 3 goals: expand on the relationship between striatin gene (STRN) status and salt-sensitivity of BP (SSBP); evaluate the status of Na+ and volume regulating systems by striatin risk allele status; evaluate potential SSBP mechanisms.

    METHODS: We assessed the relationship between STRN status in humans (HyperPATH cohort) and SSBP and on volume regulated systems in humans and a striatin knockout mouse (STRN+/-).

    RESULTS: The previously identified association between a striatin risk allele and systolic SSBP was demonstrated in a new cohort (P = 0.01). The STRN-SSBP association was significant for the combined cohort (P = 0.003; β = +5.35 mm Hg systolic BP/risk allele) and in the following subgroups: normotensives, hypertensives, men, and older subjects. Additionally, we observed a lower epinephrine level in risk allele carriers (P = 0.014) and decreased adrenal medulla phenylethanolamine N-methyltransferase (PNMT) in STRN+/- mice. No significant associations were observed with other volume regulated systems.

    CONCLUSIONS: These results support the association between a variant of striatin and SSBP and extend the findings to normotensive individuals and other subsets. In contrast to most salt-sensitive hypertensives, striatin-associated SSBP is associated with normal plasma renin activity and reduced epinephrine levels. These data provide clues to the underlying cause and a potential pathway to achieve, specific, personalized treatment, and prevention.

  3. Haas AV, En Yee L, Yuan YE, Wong YH, Hopkins PN, Jeunemaitre X, et al.
    Hypertension, 2021 Dec;78(6):1809-1817.
    PMID: 34757767 DOI: 10.1161/HYPERTENSIONAHA.121.18033
    [Figure: see text].
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