{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:03:27Z","timestamp":1785816207680,"version":"3.56.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T00:00:00Z","timestamp":1483488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004828","name":"Grand Challenges Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004828","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>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, SCNN1B) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. CYP11B2 was sequenced if the aldosterone level was high (primary aldosteronism phenotype); SCNN1B, NEDD4L, GRK4, UMOD, and NPPA genes were sequenced if the aldosterone level was low (Liddle phenotype).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>There were 14 nonsynonymous variants (NSVs) of CYP11B2: 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 GRK4 (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 SCNN1B (R206Q, G442V, and R563Q); 2 previously described and 1 associated with hypertension. NPPA was found to have 1 NSV (V32M), not previously described and NEDD4L did not have any variants. UMOD had 3 NSV: D25G, L180V, and T585I.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpw167","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T12:05:41Z","timestamp":1481025941000},"page":"478-483","source":"Crossref","is-referenced-by-count":52,"title":["High Frequency of Variants of Candidate Genes in Black Africans with Low Renin-Resistant Hypertension"],"prefix":"10.1093","volume":"30","author":[{"given":"Erika S.","family":"Jones","sequence":"first","affiliation":[{"name":"Groote Schuur Hospital, University of Cape Town 1 , Cape Town , South Africa ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. David","family":"Spence","sequence":"additional","affiliation":[{"name":"Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University 2 , London , Canada ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Mcintyre","sequence":"additional","affiliation":[{"name":"Regional Genomics Centre, Robarts Research Institute, Western University 3 , London , Canada ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Nondi","sequence":"additional","affiliation":[{"name":"Egerton University 4 , Nakuru , Kenya ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennedy","family":"Gogo","sequence":"additional","affiliation":[{"name":"Egerton University 4 , Nakuru , Kenya ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeseye","family":"Akintunde","sequence":"additional","affiliation":[{"name":"Ladoke Akintola University of Technology Teaching Hospital 5 , Ogbomoso, Oyo State , Nigeria ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Hackam","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Biostatistics and Epidemiology, Western University 6 , London , Canada ."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Rayner","sequence":"additional","affiliation":[{"name":"Groote Schuur Hospital, University of Cape Town 1 , Cape Town , South Africa ;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,4]]},"reference":[{"key":"2024020714133907900_CIT0001","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/00001648-200301000-00029","article-title":"Salt, slavery and survival- hypertension in the African diaspora","volume":"14","author":"Grim","year":"2003","journal-title":"Epidemiology"},{"key":"2024020714133907900_CIT0002","first-page":"e29","article-title":"Heart disease and stroke statistics\u20132015 update: a report from the American Heart Association","volume":"131","author":"Mozaffarian","year":"2015","journal-title":"Circulation"},{"key":"2024020714133907900_CIT0003","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1161\/01.STR.0000217222.09978.ce","article-title":"Racial and geographic differences in awareness, treatment, and control of hypertension: the REasons for Geographic And Racial Differences in Stroke study","volume":"37","author":"Howard","year":"2006","journal-title":"Stroke"},{"key":"2024020714133907900_CIT0004","first-page":"1286","article-title":"The association of the R563Q genotype of the ENaC with phenotypic variation in Southern Africa","volume":"25","author":"Jones","year":"2012","journal-title":"Am J Hypertens"},{"key":"2024020714133907900_CIT0005","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/jhh.2011.33","article-title":"G-protein-coupled receptor kinase 4 polymorphisms predict blood pressure response to dietary modification in Black patients with mild-to-moderate hypertension","volume":"26","author":"Rayner","year":"2012","journal-title":"J Hum Hypertens"},{"key":"2024020714133907900_CIT0006","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1136\/jmg.37.11.831","article-title":"A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22)","volume":"37","author":"Lafferty","year":"2000","journal-title":"J Med Genet"},{"key":"2024020714133907900_CIT0007","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1097\/00004872-200018090-00002","article-title":"Primary aldosteronism: learning from the study of familial varieties","volume":"18","author":"Stowasser","year":"2000","journal-title":"J Hypertens"},{"key":"2024020714133907900_CIT0008","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1161\/01.HYP.0000203771.24792.bf","article-title":"Individualized therapy for hypertension","volume":"47","author":"Spence","year":"2006","journal-title":"Hypertension"},{"key":"2024020714133907900_CIT0009","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.1210\/jcem.86.8.9995","article-title":"Prevalence of primary aldosteronism in unselected hypertensive populations: screening and definitive diagnosis","volume":"86","author":"Ganguly","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2024020714133907900_CIT0010","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/sj.jhh.1001182","article-title":"T594M and G442V polymorphisms of the sodium channel beta subunit and hypertension in a black population","volume":"15","author":"Dong","year":"2001","journal-title":"J Hum Hypertens"},{"key":"2024020714133907900_CIT0011","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1161\/HYPERTENSIONAHA.112.198721","article-title":"G protein receptor kinase 4 polymorphisms: \u03b2-blocker pharmacogenetics and treatment-related outcomes in hypertension","volume":"60","author":"Vandell","year":"2012","journal-title":"Hypertension"},{"key":"2024020714133907900_CIT0012","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1365-2265.2008.03383.x","article-title":"Effects of genetic variation in the aldosterone synthase (CYP11B2) gene on enzyme function","volume":"70","author":"Holloway","year":"2009","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024020714133907900_CIT0013","doi-asserted-by":"crossref","first-page":"4996","DOI":"10.1073\/pnas.89.11.4996","article-title":"Mutations in the human CYP11B2 (aldosterone synthase) gene cousing corticosterone methyloxidase II deficiency","volume":"89","author":"Pascoe","year":"1992","journal-title":"Proc Nat Acad Sci"},{"key":"2024020714133907900_CIT0014","first-page":"255","article-title":"A missense mutation (GGC[435Gly]\u2013&gt;AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism","volume":"60","author":"Kuribayashi","year":"2003","journal-title":"Horm Res"},{"key":"2024020714133907900_CIT0015","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1161\/01.HYP.0000217521.79447.9a","article-title":"Emergence of novel genetic effects on blood pressure and hemodynamics in adolescence: the Georgia Cardiovascular Twin Study","volume":"47","author":"Kupper","year":"2006","journal-title":"Hypertension"},{"key":"2024020714133907900_CIT0016","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1097\/HJH.0b013e328337f6bc","article-title":"Genome-wide case\/control studies in hypertension: only the \u2018tip of the iceberg\u2019","volume":"28","author":"Zhang","year":"2010","journal-title":"J Hypertens"}],"container-title":["American Journal of Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajh\/article\/30\/5\/478\/2806644","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/article\/30\/5\/478\/2806644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T17:31:29Z","timestamp":1707327089000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajh\/article\/30\/5\/478\/2806644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,4]]},"references-count":16,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,1,4]]},"published-print":{"date-parts":[[2017,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ajh\/hpw167","relation":{},"ISSN":["0895-7061","1941-7225"],"issn-type":[{"value":"0895-7061","type":"print"},{"value":"1941-7225","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,5,1]]},"published":{"date-parts":[[2017,1,4]]}}}