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Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 239))

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Abstract

High blood pressure is a common and major risk factor for cardiovascular disease. Still, the pathogenesis of essential hypertension remains incompletely understood. It is generally felt that different factors may contribute in an individual patient. Among those that have been intensively studied are salt intake, obesity and insulin resistance, the renin-angiotensin system, and the sympathetic nervous system. In the past few years, research has been increasingly directed towards the genetics of hypertension.

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References

  1. Lander E.S., Schork N.J. Genetic dissection of complex traits. Science 1994; 265:2037–48.

    Article  PubMed  CAS  Google Scholar 

  2. Dykes C.W. Genes, disease and medicine. Br J Clin Pharmacol 1996; 42:683–95.

    Article  PubMed  CAS  Google Scholar 

  3. Reed P.W., Davies J.L., Copeman J.B., et al. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nat Genet 1994; 7:390–5.

    Article  PubMed  CAS  Google Scholar 

  4. Todd J.A. Genetic analysis of type 1 diabetes using whole genome approaches. Proc Nat Acad Sci USA 1995; 92:8560–5.

    Article  PubMed  CAS  Google Scholar 

  5. Lifton R.P. Molecular genetics of human blood pressure variation. Science 1996; 272:676–80.

    Article  PubMed  CAS  Google Scholar 

  6. Kaplan N.M. Primary hypertension: pathogenesis. In: Kaplan NM (ed). Clinical Hypertension, 7th ed. Baltimore, Williams & Wilkins, 1998, p. 42.

    Google Scholar 

  7. Woolfson R.G., de Wardener H.E. Primary renal abnormalities inhereditary hypertension. Kidney Int 1996; 50:717–31.

    Article  PubMed  CAS  Google Scholar 

  8. Guidi E., Menghetti D., Milani S., et al. Hypertension may be tranplanted with the kidney in humans: A long-term historical perspective follow-up of recipients grafted with kidneys coming from donors with or without hypertension in their families. J Am Soc Nephrol 1996; 7:1131–8.

    PubMed  CAS  Google Scholar 

  9. Sutherland D.J., Ruse J.L., Laidlaw J.C. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J 1996; 95: 1109–19.

    Google Scholar 

  10. Lifton R.P., Dluhy R.G., Powers M., et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355:262–5.

    Article  PubMed  CAS  Google Scholar 

  11. Litchfield W.R., Coolidge C., Silva P., et al. Impaired potassium-stimulated aldosterone production: A possible explanation for normokalemic glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 1997; 82:1507–10.

    Article  PubMed  CAS  Google Scholar 

  12. Jonsson J.R., Klemm S.A., Tunny T.J., et al. A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. Biochem Biophys Res Comm 1995; 207:565–71.

    Article  PubMed  CAS  Google Scholar 

  13. White P.C. Inherited forms of mineralocorticoid hypertension. Hypertension 1996; 28:927–36.

    Article  PubMed  CAS  Google Scholar 

  14. Mune T, Rogerson F.M., Nikkila H, et al. Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase. Nat Genet 1995; 10:394–9.

    Article  PubMed  CAS  Google Scholar 

  15. Dave-Sharma S, Wilson R.C., Harbison M.D., et al. Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab 1998; 83:2244–54.

    Article  PubMed  CAS  Google Scholar 

  16. White P.C., Mune T., Agrawal A.K. 11-Hydroxysteroiddehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocr Rev 1997; 18: 135–56.

    Article  PubMed  CAS  Google Scholar 

  17. Liddie G.W., Bledsoe T, Coppage W.S. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Physicians 1963; 76:199–213.

    Google Scholar 

  18. Kellenberger S, Gautschi I, Rossier B.C., Schild L. Mutations causing Liddie syndrome reduce sodium-dependent downregulation of the epithelial sodium channels in the Xenopus oocyte expression system. J Clin Invest 1998; 101:2741–50.

    Article  PubMed  CAS  Google Scholar 

  19. Shimkets R. Wamock D.G., Bositis C.M., et al. Liddie’ s syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell1994; 79:407–14.

    Article  PubMed  CAS  Google Scholar 

  20. Gordon R.D., Geddes R.A., Pawsey C.G., et al. Hypertension and severe hyperkalaemia associated with supression of renin and aldosterone and completely reversed by dietary sodium restriction. Austral Ann Med 1970; 19:287–94.

    CAS  Google Scholar 

  21. Mansfield T.A., Simon D.B., Farfel Z, et al. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type H, to chromosomes 1 q31-42 and 17p l1-q2l. Nat Genet 1997; 16:202–5.

    Article  PubMed  CAS  Google Scholar 

  22. Julier C, Delepine M, Keaveney B, et al. Genetic susceptibility for human familial essential hypertension in a region of homology with blood pressure linkage on rat chromosome 10. Hum Mol Genet 1997; 6:2077–85.

    Article  PubMed  CAS  Google Scholar 

  23. Wong Y, Stebbing M, Ellis J.A., et al. Genetic linkage of beta and gamma subunits of epithelial sodium channel to systolic blood pressure. Lancet 1999; 353: 1222–5.

    Article  PubMed  CAS  Google Scholar 

  24. Ambrosius W.T., Bloem L.J., Zhou L., et al. Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension. Hypertension 1999; 34:631–7.

    Article  PubMed  CAS  Google Scholar 

  25. Melander O, Orho M, Fagerudd J, et al. Mutations and variants of the epithelial sodium channel gene in Liddle’s syndrome and primary hypertension. Hypertension 1998; 31:1118–24.

    Article  PubMed  CAS  Google Scholar 

  26. Wamock D.G.. Aldosterone-related genetic effects in hypertension. Curr Hypertens Rep 2000; 2:295–301.

    Article  Google Scholar 

  27. Bonnardeaux A., Nadaud S., Charru A., et al. Lack of evidence fr linkage of the endothelial nitric oxide synthase gene to essential hypertension. Circulation 1995; 91:96–102.

    Article  PubMed  CAS  Google Scholar 

  28. Staessen J.A., Kuznetsova T., Wang J.G., et al. M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J Hypertens 1999; 17:9–17.

    Article  PubMed  CAS  Google Scholar 

  29. Ishigami T, Umemura S, Iwamoto T, et al. Molecular variant of angiotensinogen gene is associated with coronary atherosclerosis. Circulation 1995; 91:951–4.

    Article  PubMed  CAS  Google Scholar 

  30. Ward K, Hata A, Jeunemaitre X, et al. A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 1993; 4:59–61.

    Article  PubMed  CAS  Google Scholar 

  31. Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of hypertension: role of angiotensinogen. Cell1992; 71:169–80.

    Article  PubMed  CAS  Google Scholar 

  32. Caulfield M. Lavender P. Farrall M, et al. Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 1994; 330:1629–33.

    Article  PubMed  CAS  Google Scholar 

  33. Caulfield M. Lavender P. Newell-Price J, et al. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Cin lnvest 1995; 96:687–92.

    Article  CAS  Google Scholar 

  34. Schunkert H. Hense H-W, Gimenez-Roqueplo A, et al. The angiotensinogen T235 variant and the uSe of antihypertensive drugs in a population-based cohort. Hypertension 1997; 29:628–33.

    Article  PubMed  CAS  Google Scholar 

  35. Hingorani A.D., Sharrna P. Jia H. et al. Blood pressure and the M235T polymorphism of the angiotensinogen gene. Hypertension 1996; 28:907–11.

    Article  PubMed  CAS  Google Scholar 

  36. Jeunemaitre X. Inoue I. Williams C. et al. Haplotypes of angiotensinogen in essential hypertension. Am J Hum Genet 1997; 60: 1448–60.

    Article  PubMed  CAS  Google Scholar 

  37. Inoue I. Nakajima T. Williams C. et al. A nucleotide substitution in the promotor of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin lnvest 1997; 99: 1786–97.

    Article  CAS  Google Scholar 

  38. Hunt S.C., Coole N.R., Oberrnan A. et al. Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension (Trials of Hypertension Prevention, phase II). Hypertension 1998; 32:393–401.

    Article  PubMed  CAS  Google Scholar 

  39. Brand E. Chatelain N. Keavney B. et al. Evaluation of the angiotensinogen locus in human essential hypertension: a European study. Hypertension 1998; 31:725–9.

    Article  PubMed  CAS  Google Scholar 

  40. Dudley C. Keavney B. Casadei B. et al. Prediction of patient responses to antihypertensive drugs using genetic polymorphisms: investigation of renin-angiotensin system genes. J Hypertens 1996; 14:259–62.

    Article  PubMed  CAS  Google Scholar 

  41. Hingorani A.D., Jia H., Stevens P., et al. Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition. J Hypertens 1995; 13: 1602–9.

    PubMed  CAS  Google Scholar 

  42. Tiret L. Rigat B. Visvikis S. et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 1992; 51:197–205.

    PubMed  CAS  Google Scholar 

  43. Cambien F. Alhenc-Gelas F. Herbeth B. et al. Familial resemblance of plasma angiotensinconverting enzyme levels: the Nancy study. Am J Hum Genet 1988; 43:774–80.

    PubMed  CAS  Google Scholar 

  44. Staessen J.A., Wang J.G., Ginocchio G. et al. The deletionIinsertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J Hypertens 1997; 15:1579–92.

    Article  PubMed  CAS  Google Scholar 

  45. Agerholm-Larsen B, Nordestgaard B.G., Tybjærg-Hansen. ACE gene polymorphism in cardiovascular disease. Meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol2000; 20:484–92.

    CAS  Google Scholar 

  46. Keavney B, McKenzie C, Parish S, et al. Large-seale test of hypothesised associations between the angiotensin-eonverting-enzyme insertion/deletion polymorphism and myocardial infaretion in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators. Lancet 2000; 355:434–42.

    CAS  Google Scholar 

  47. Sasaki M, Takashi O, Luehi A, et al. Relationship between the angiotensin converting enzyme gene polymorphism and the effects of enalapril on left ventricular hypertrophy and impaired diastolic filling in essential hypertension: M-mode and pulsed doppler echocardiographic studies. J Hypertens 1996; 14:1403–8.

    Article  PubMed  CAS  Google Scholar 

  48. Bonnardeaux A, Davies E, Jeunemaitre X, et al. Angiotensin II (type I) receptor gene polymorphisms in human essential hypertension. Hypertension 1994; 24:63–9.

    Article  PubMed  CAS  Google Scholar 

  49. Benetos A, Topouchian J, Rieard S, et al. Influence of angiotensin II type I receptor polymophism on aortic stiffness in never-treated hypertensive patients. Hypertension 1995; 26:44–7.

    Article  PubMed  CAS  Google Scholar 

  50. Spiering W, Kroon A.A., Fuss-Lejeune M.M.J.J., et al. Sensitivity, but not reactivity to angiotensin II is associated with the angiotensin II type 1 receptor A1166C polymorphism. Hypertension 2000; 36:411–16.

    Article  PubMed  CAS  Google Scholar 

  51. Diegeuz-Lucena J.L., Aranda-Lara P, Ruiz-Galdon M, et al. Angiotensin I-converting enzyme genotypes and angiotensin II receptors-respons to therapy. Hypertension 1996; 28:98-103.

    Google Scholar 

  52. Staessen J.A., Kuznetsova T, Wang J.G., et al. M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J Hypertens 1999; 17:9–17.

    Article  PubMed  CAS  Google Scholar 

  53. Benetos A, Cambien F, Gautier S, et al. Influence of angiotensin II type I receptor gene polymorphism on the effeets of peridopril and nitrendipine on arterial stiffuess in hypertensive individuals. Hypertension 1996; 28:1081–4.

    Article  PubMed  CAS  Google Scholar 

  54. Kawamoto T, Mitsuuchi Y, Toda K, et al. Role of steroid 11ß-hydroxylase and steroid 18-hydroxyl ase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. Proe Natl Acad Sci USA 1992; 89:1458–62.

    Article  CAS  Google Scholar 

  55. Curnow K.M., Tusie-Luna M.T., Pascoe L, et al. The product of the CYPIIB2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Mol Endocrinol 1991; 5: 1513–22.

    Article  PubMed  CAS  Google Scholar 

  56. Chua S.C., Szabo P, Vitek A. et al. Cloning of cDNA eneoding steroid 11ß-hydroxylase (P450cll). Proc Natl Acad Sci USA 1987; 84:7193–7.

    Article  PubMed  CAS  Google Scholar 

  57. Wagner M.J., Ge Y, Siciliano M, Wells D.E. A hybrid cell mapping panel for regional loealization of probes to human chromosome 8. Genomies 1991; 10: 114–25.

    Article  CAS  Google Scholar 

  58. White P.C., New M.I., Dupont B. Congenital adrenal hyperplasia. Part 1. N Engl J Med 1987; 316:1519–24.

    Article  CAS  Google Scholar 

  59. White P.C., New M.I., Dupont B. Congenital adrenal hyperplasia. Part 2. N Engl J Med 1987; 316: 1580–6.

    CAS  Google Scholar 

  60. Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation of the aldosterone synthase gene in hypertension. Hypertension 1998; 32:198–204.

    Article  PubMed  CAS  Google Scholar 

  61. Weinberger M.H., Miller J.Z., Luft F.C., Grim C.E., Fineberg N.S. Definitions and eharaeteristies of sodium sensitivity and blood pressure resistance. Hypertension 1986; 8(suppl II): 127–34.

    Google Scholar 

  62. De la Sierra A, Luch M.M., Coca A, et al. Fluid, ionic and hormonal changes induced by high salt intake in salt-sensitives and salt-resistant hypertensive patients. Clin Sci 1996; 91: 155–61.

    PubMed  Google Scholar 

  63. Giner V, Poch E, Bragulat E, et al. Renin-angiotensin system genetic polymorphisms and saltsensitivity in essential hypertension. Hypertension 2000; 35:512–7.

    Article  PubMed  CAS  Google Scholar 

  64. Matsuoka Y, Hughes C.A., Bennet V. Adducin regulation. Definition of the calmodulin-binding domaili and sites of phosphorylation by protein kinases A and C. J Biol Chem 1996; 271:25157–66.

    Article  PubMed  CAS  Google Scholar 

  65. Huges C.A., Bennett V. Adducin: a physical model with implieations for function in assembly of speetrin-actin complexes. J Biol Chem 1995; 270: 18990–6.

    Article  Google Scholar 

  66. Ferrandi M, Salardi S, Tripodi G, et al. Evidance for an interaction between adducin and Na(+)-K(+)-ATPase: relation to genetic hypertension. Am J Physiol 1999; 277:H1338–49.

    Google Scholar 

  67. Cusi D, Barlassina C, Azzani T, et al. Polymorphisms of alpha adducin and salt sensitivity in patients with essential hypertension. Lancet 1997; 349: 1353–7.

    Article  PubMed  CAS  Google Scholar 

  68. Kamitani A, Wong Z.Y., Frasser R, et al. Human alpha-adducin gene, blood pressure, and sodium metabolism. Hypertension 1998; 32:l38–43.

    Article  Google Scholar 

  69. Kato N, Sugiyama T, Nakiba T, et al. Lack of association between the alpha-adducin locus and essential hypertension in the Japanese population. Hypertension 1998; 32:730–3.

    Article  Google Scholar 

  70. Beeks E, Janssen R.G.J.H., Kroon A.A., et al. Association between the alpha-adducin Gly460Trp polymorphism and blood pressure in familial combined hyperlipidemia. Hypertension 2000; 36:668 (abstract).

    Google Scholar 

  71. Siffert W, Rosskopf D, Siffert G, et al. Association of a human G-protein 3 subunit variant with hypertension. Nat Genet 1998; 18:45–8.

    Article  PubMed  CAS  Google Scholar 

  72. Rosskopf D, Busch S, Manthey I, Siffert W.G. protein beta 3 gene: structure, promoter, and additional polymorphisms. Hypertension. 2000; 36:33–41.

    Article  PubMed  CAS  Google Scholar 

  73. Siffert W, Forster P, Jockei K.H., et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephrol 1999; 10:1921–30.

    PubMed  CAS  Google Scholar 

  74. Brand E, Herrmann S.M., Nicaud V, et al. The 825C/T polymorphism of the G-protein subunit beta3 is not related to hypertension. Hypertension. 1999; 33: 1175-8.

    Google Scholar 

  75. Poch E, Gonzalez D, Gomez-Angelats E, et al. G-Protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension. Hypertension. 2000; 35(IPt2):214–8.

    Article  PubMed  CAS  Google Scholar 

  76. Sevetkey L.P., Timmons P.Z., Emovon O, et al. Association of hypertension with beta2-and alpha2-adrenergic receptor genotype. Hypertension 1996; 27:1210–5.

    Article  Google Scholar 

  77. Jia H, Hingorani A.D., Sharma P, et al. Association of the G, gene with essential hypertension and response to-blockade. Hypertension 1999; 34:8–14.

    Article  PubMed  CAS  Google Scholar 

  78. Bray M.S., Boerwinkle E. The role of 2-adrenergic receptor variation in human hypertension. Curr Hypertens Rep 2000; 2:39–43.

    Article  PubMed  CAS  Google Scholar 

  79. Kotanko P, Binder A, Tasker J, et al. Essential hypertension in African Caribbeans associates with a variant of the beta,-adrenoceptor. Hypertension 1997; 30:773–6.

    Article  PubMed  CAS  Google Scholar 

  80. Lang C.C., Stein M, Brown M, et al. Attenuation of isoproterenol-mediated vasodilatation in blacks. N Engl J Med 1995; 333: 155–60.

    Article  PubMed  CAS  Google Scholar 

  81. Klungel O.H., Stricker B.H.C., Paes A.H.P., et al. Excess stroke among hypertensive men and women due to undertreatment of hypertension. Stroke 1999; 30: 1312–8.

    Article  PubMed  CAS  Google Scholar 

  82. Kaplan R.C., Psaty B.M., Heckbert S.R., et al. Blood pressure level and incidence of myocardial infarction among patients treated for hypertension. Am J Public Health 1999; 89: 1414–7.

    Article  PubMed  CAS  Google Scholar 

  83. Weder A.B. Selecting the right drug for initial antihypertensive therapy. Curr Hypertens Rep 2000; 2: 13–5.

    Article  PubMed  CAS  Google Scholar 

  84. Drews J. Drug discovery: a historie al perspective. Science 2000; 287: 1960–4.

    Article  PubMed  CAS  Google Scholar 

  85. Evans W.E., Relling M.V. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286:487–91.

    Article  PubMed  CAS  Google Scholar 

  86. Neaton J.D., Grimm R.H. Jr., Prineas RJ, et al. Treatment of Mild Hypertension Study. Final results Treatment of Mild Hypertension Study Group. JAMA 1993; 270:713–24.

    CAS  Google Scholar 

  87. Blood Pressure Lowering Treatment Trialists’Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs:results of prospective1y designed overviews of randomised trials. Lancet 2000; 355:1955–64.

    Article  Google Scholar 

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Kroon, A.A., Spiering, W., de Leeuw, P.W. (2001). Genetics of Hypertension. In: Doevendans, P.A., Wilde, A.A.M. (eds) Cardiovascular Genetics for Clinicians. Developments in Cardiovascular Medicine, vol 239. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-1019-1_4

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