High Frequency of Variants of Candidate Genes in Black Africans with Low Renin-Resistant Hypertension

<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">OBJECTIVES</div>Black subjects tend to retain salt and water, be more sensitive to aldosterone, and have suppression of plasma renin activity. Variants of the renal sodium channel (ENaC, <span style="font-style:italic;">SCNN1B</span>) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important.<div class="boxTitle">METHODS</div>Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. <span style="font-style:italic;">CYP11B2</span> was sequenced if the aldosterone level was high (primary aldosteronism phenotype); <span style="font-style:italic;">SCNN1B</span>, <span style="font-style:italic;">NEDD4L</span>, <span style="font-style:italic;">GRK4</span>, <span style="font-style:italic;">UMOD</span>, and <span style="font-style:italic;">NPPA</span> genes were sequenced if the aldosterone level was low (Liddle phenotype).<div class="boxTitle">RESULTS</div>There were 14 nonsynonymous variants (NSVs) of <span style="font-style:italic;">CYP11B2</span>: 3 previously described and associated with alterations in aldosterone synthase production (R87G, V386A, and G435S). Out of 14, 9 variants were found in all 9 patients sequenced. There were 4 NSV of <span style="font-style:italic;">GRK4</span> (R65L, A116T, A142V, V486A): at least one was found in all 9 patients; 3 were previously described and associated with hypertension. There were 3 NSV of <span style="font-style:italic;">SCNN1B</span> (R206Q, G442V, and R563Q); 2 previously described and 1 associated with hypertension. <span style="font-style:italic;">NPPA</span> was found to have 1 NSV (V32M), not previously described and <span style="font-style:italic;">NEDD4L</span> did not have any variants. <span style="font-style:italic;">UMOD</span> had 3 NSV: D25G, L180V, and T585I.<div class="boxTitle">CONCLUSIONS</div>A phenotypic approach to investigating the genetic architecture of RHT uncovered a surprisingly high yield of variants in candidate genes. These preliminary findings suggest that this novel approach may assist in understanding the genetic architecture of RHT in Blacks and explain their two fold risk of stroke.</span>

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