2.3.3. *SCNN1B* and *NEED4*

Activation of ENaC, either due to structural variants of the channel subunits (e.g.,: *SCNN1B*) or altered activity of regulatory processes (including *NEED4*), could underlie low-renin hypertension in African Americans. One study showed that ENaC channel activity, as assessed by nasal transmucosal electrical potential difference, was greater in African Americans than in whites [69]. In a mixed ancestry population of South Africans, a variant in *SCNN1B* (p.R563Q) was present in 18 people, of whom 17 were hypertensive [50]. In another study, this variant was present in 6% of Africans from urban South Africa that responded to treatment with amiloride therapy [70]. This variant was associated with a resistant form of hyporeninemic hypoaldosteronism hypertension, analogous to Liddle syndrome. Moreover, the p.T594M but not p.G442V (which causes lower aldosterone secretion, suggesting increased ENaC activity) variants in *SCNN1B* may also contribute to hypertension in African Americans [71]. In another study, individuals with variants in *NEDD4* were linked to increased BP and adverse cardiovascular outcomes [20,72,73].
