title: High Frequency of Variants of Candidate Genes in Black Africans with Low Renin-Resistant Hypertension.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Erika S
authors.initials: ES
authors.lastname: Jones
authors.affiliation: Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Spence
authors.affiliation: Regional Genomics Centre, Robarts Research Institute, Western University, London, Canada.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Mcintyre
authors.affiliation: Egerton University, Nakuru, Kenya.
authors.forename: Justus
authors.initials: J
authors.lastname: Nondi
authors.affiliation: Egerton University, Nakuru, Kenya.
authors.forename: Kennedy
authors.initials: K
authors.lastname: Gogo
authors.affiliation: Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, Oyo State, Nigeria.
authors.forename: Adeseye
authors.initials: A
authors.lastname: Akintunde
authors.affiliation: Departments of Medicine and Biostatistics and Epidemiology, Western University, London, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Hackam
authors.affiliation: Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Rayner
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000235:genetics; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000235:genetics; D005260:Female; D054771:G-Protein-Coupled Receptor Kinase 4 / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D010641:Phenotype; D011379:Prognosis; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System; D018570:Risk Assessment; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D020521:Stroke / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D058949:Uromodulin / Q000235:genetics
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D005819:Genetic Markers; C472955:NPPA protein, human; C507048:SCNN1B protein, human; C548612:UMOD protein, human; D058949:Uromodulin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D019405:Cytochrome P-450 CYP11B2; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human; D012083:Renin
keywords: CYP11B2; GRK4; NEDD4L; NPPA; SCNN1B; UMOD.; blood pressure; candidate genes; hypertension