Human Essential Hypertension: Role of the Genes of the Renin-Aldosterone System

  • X. Jeunemaitre
  • S. Disse-Nicodème
  • A. Gimenez-Roqueplo
  • P. Corvol
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 242)


A number of epidemiologic studies have shown that individual blood pressure levels result from both genetic predisposition and environmental factors. It is generally accepted that approximately 30% of the variance of blood pressure is attributable to genetic heritability and 50% to environmental influences [1].


Essential Hypertension 235T Allele Renin Gene Angiotensinogen Gene Human Essential Hypertension 
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  1. 1.
    Ward R. Familial aggregation and genetic epidemiology of blood pressure. In “Hypertension: Pathophysiology, Diagnosis and Management”.Laragh JH and BrennerBMEds Raven Press Ltd New York1990:81–100.Google Scholar
  2. 2.
    Corvol P, Soubrier F, Jeunemaitre X. Molecular genetics of the renin-angiotensinaldosterone system in human hypertension. Pathol Biol (Paris) 1997;45:229–39.Google Scholar
  3. 3.
    Rieder MJ, Nickerson DA. Hypertension and single nucleotide polymorphisms. Curr Hypertens Rep 2000;2:44–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Danser AH, Schunkert H. Renin-angiotensin system gene polymorphisms: potential mechanisms for their association with cardiovascular diseases. Eur J Pharmacol 2000;410:303–16.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang JG, Staessen JA. Genetic polymorphisms in the renin-angiotensin system: relevance for susceptibility to cardiovascular disease. Eur J Pharmacol 2000;410:289–302.PubMedCrossRefGoogle Scholar
  6. 6.
    Rapp JP, Wang SM, Dene H. A genetic polymorphism in the renin gene of Dahl rats cosegregates with blood pressure. Science 1989;243:542–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Grim CE, Luft FC, Miller JZ, et al. An approach to the evaluation of genetic influences on factors that regulate arterial blood pressure in man. Hypertension 1980;2[suppl2l:I-34–42.CrossRefGoogle Scholar
  8. 8.
    Soubrier F, Jeunemaitre X, Rigat B, et al. Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects. Hypertension 1990;16:712–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Jeunemaitre X, Rigat B, Charru A, et al. Sib pair linkage analysis of renin gene haplotypes in human essential hypertension. Hum Genet 1992;88:301–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Cambien F, Alhenc-Gelas F, Herbeth B, et al. Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study. Am J Hum Genet 1988;43:77480.Google Scholar
  11. 11.
    Rigat B, Hubert C, Alhenc-Gelas F, et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–13466.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedGoogle Scholar
  13. 13.
    Rieder MJ, Taylor SL, Clark AG, et al. Sequence variation in the human angiotensin converting enzyme. Nat Genet 1999;22:59–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Hilbert P, Lindpaintner K, Beckmann JS, et al. Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature 1991;353:521–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Jacob HJ, Lindpaintner K, Lincoln SE, et al. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 1991;67:213–24.PubMedCrossRefGoogle Scholar
  16. 16.
    O’Donnell CJ, Lindpaintner K, Larson MG, et al. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 1998;97:1766–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Fornage M, Amos Cl, Kardia S, et al. Variation in the region of the angiotensinconverting enzyme gene influences interindividual differences in blood pressure levels in young white males. Circulation 1998;97:1773–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Julier C, Delepine M, Keavney 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.PubMedCrossRefGoogle Scholar
  19. 19.
    Staessen JA, Wang JG, Brand E, et al. Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens 2001;19:1349–58.PubMedCrossRefGoogle Scholar
  20. 20.
    Jeunemaitre X, Soubrier F, Kotelevtsev YV, et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992;71:169–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Caulfield M, Lavender P, Farrall M, et al. Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 1994;330:1629–33.PubMedCrossRefGoogle Scholar
  22. 22.
    Caulfield M, Lavender P, Newell-Price J, et al. Angiotensinogen in human essential hypertension. Hypertension 1996;28:1123–5.PubMedCrossRefGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    Caulfield M, Lavender P, Newell-Price J, et al. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest 1995;96:68792.CrossRefGoogle Scholar
  25. 25.
    Atwood LD, Kammerer CM, Samollow PB, et al. Linkage of essential hypertension to the angiotensinogen locus in Mexican Americans. Hypertension 1997;30:326–30.PubMedCrossRefGoogle Scholar
  26. 26.
    Niu T, Xu X, Rogus J, et al. Angiotensinogen gene and hypertension in Chinese. J Clin Invest 1998;101:188–94.PubMedCrossRefGoogle Scholar
  27. 27.
    Rotimi C, Morrison L, Cooper R, et al. Angiotensinogen gene in human hypertension. Lack of an association of the 235T allele among African Americans.Hypertension1994;24:591–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Jeunemaitre X, Gimenez-Roqueplo AP, Celerier J, et al. Angiotensinogen variants and human hypertension. Curr Hypertens Rep 1999;1:31–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Kunz R, Kreutz R, Beige J, et al. Association between the angiotensinogen 235T-variant and essential hypertension in whites: a systematic review and methodological appraisal. Hypertension 1997;30:1331–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Staessen JA, Kuznetsova T, Wang JG, et al. M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J Hypertens 1999;17:9–17.PubMedCrossRefGoogle Scholar
  31. 31.
    Sethi AA, Tybjaerg-Hansen A, Gronholdt ML, et al. Angiotensinogen mutations and risk for ischemic heart disease, myocardial infarction, and ischemic cerebrovascular disease. Six case-control studies from the Copenhagen City Heart Study. Ann Intern Med 2001;134:941–54.PubMedGoogle Scholar
  32. 32.
    Bloem LJ, Manatunga AK, Tewksbury DA, et al. The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children. J Clin Invest 1995;95:948–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Schunkert H, Hense HW, Gimenez-Roqueplo AP, et al. The angiotensinogen T235 variant and the use of antihypertensive drugs in a population-based cohort. Hypertension 1997;29:628–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Bloem LJ, Foroud TM, Ambrosius WT, et al. Association of the angiotensinogen gene to serum angiotensinogen in blacks and whites. Hypertension 1997;29:1078–82.PubMedCrossRefGoogle Scholar
  35. 35.
    Smithies O, Kim HS. Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice. Proc Nat1 Acad Sci USA 1994;91:3612–5.CrossRefGoogle Scholar
  36. 36.
    Inoue I, Nakajima T, Williams CS, et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997;99:1786–97.PubMedCrossRefGoogle Scholar
  37. 37.
    Ward K, Hata A, Jeunemaitre X, et al. A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 1993;4:59–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Arngrimsson R, Purandare S, Connor M, et al. Angiotensinogen: a candidate gene involved in preeclampsia? Nat Genet 1993;4:114–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Bonnardeaux A, Davies E, Jeunemaitre X, et al. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994;24:63–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Zhang X, Erdmann J, Regitz-Zagrosek V, et al. Evaluation of three polymorphisms in the promoter region of the angiotensin Il type I receptor gene. J Hypertens 2000;18:267–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Kainulainen K, Perola M, Terwilliger J, et al. Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension. Hypertension 1999;33:844–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Perola M, Kainulainen K, Pajukanta P, et al. Genome-wide scan of predisposing loci for increased diastolic blood pressure in Finnish siblings. J Hypertens 2000;18:1579–85.PubMedCrossRefGoogle Scholar
  43. 43.
    Vuagnat A, Giacche M, Hopkins PN, et al. Plasma LDL cholesterol is a strong redictor of the blood pressure increase following an acute infusion of angiotensin II. J Mol Med 2001 79:175–183PubMedCrossRefGoogle Scholar
  44. 44.
    Brand E, Chatelain N, Mulatero P, et al. Structural analysis and evaluation of the aldosterone synthase gene in hypertension. Hypertension 1998;32:198–204.PubMedCrossRefGoogle Scholar
  45. 45.
    Davies E, Holloway CD, Ingram MC, et al. Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension 1999;33:703–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Komiya I, Yamada T, Takara M, et al. Lys(173)Arg and -344T/C variants of CYP11B2 in Japanese patients with low-renin hypertension. Hypertension 2000;35:699–703.PubMedCrossRefGoogle Scholar
  47. 47.
    Mulatero P, Schiavone D, Fallo F, et al. CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism. Hypertension 2000;35:694–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Clyne CD, Zhang Y, Slutsker L, et al. Angiotensin Il and potassium regulate human CYP11B2 transcription through common cis-elements. Mol Endocrinol 1997;11:638–49.PubMedCrossRefGoogle Scholar
  49. 49.
    Hautanena A, Lankinen L, Kupari M, et al. Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males. J Intern Med 1998;244:118.Google Scholar
  50. 50.
    Kupari M, Hautanen A, Lankinen L, et al. Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation 1998;97:569–75.PubMedCrossRefGoogle Scholar
  51. 51.
    Schunkert H, Hengstenberg C, Holmer SR, et al. Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. Circulation 1999;99:2255–60.PubMedCrossRefGoogle Scholar
  52. 52.
    Hautanen A, Toivanen P, Manttari M, et al. Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction. Circulation 1999;100:2213–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Tamaki S, Iwai N, Tsujita Y, et al. Genetic polymorphism of CYPI1B2 gene and hypertension in Japanese. Hypertension 1999;33:266–70.PubMedCrossRefGoogle Scholar
  54. 54.
    Williams SM, Addy JH, Phillips JA, et al. Combinations of variations in multiple genes are associated with hypertension. Hypertension 2000;36:2–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • X. Jeunemaitre
  • S. Disse-Nicodème
  • A. Gimenez-Roqueplo
  • P. Corvol

There are no affiliations available

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