Abstract
Blood pressure is a quantitative trait that varies continuously throughout the whole population and whose regulation is controlled by a variety of mechanisms that involve several genetic loci and environmental factors. However, little is known about the genes actually involved in human hypertension, about their respective importance in determining blood pressure level, and their interaction with other genes and environmental components. A number of epidemiologic studies have shown that individual blood pressure levels result from both genetic predisposition and environmental factors. The heritable component of blood pressure has been documented in familial and twin studies. The evidence suggests that approximately 30% of the variance of blood pressure is attributable to genetic heritability and 50% to environmental influences (Ward 1990).
Chapter PDF
Similar content being viewed by others
Keywords
- Human Hypertension
- Epithelial Sodium Channel
- Renin Angiotensin Aldosterone System
- Renin Gene
- Angiotensinogen Gene
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH (1991) Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. New Engl J Med 324: 1098–1104
Alhenc-Gelas F, Richard J, Courbon D, Warnet JM, Corvol P (1991) Distribution of plasma angiotensin I converting enzyme levels in healthy men: relationship to environmental and hormonal parameters. J Lab Clin Med 117: 33–39
Arngrimsson R, Purandare S, Connor M, Walker JJ, Björnsson S, Soubrier F, Kotelevtsev Y, Geirsson RT, Björnsson H (1993) Angiotensinogen: a candidate gene involved in preeclampsia. Nature Genet 4: 114–115
Barley J, Blackwood A, Carter ND, Crews DE, Cruickshank JK, Jeffery S, Ogunlesi AO, Saguella GA (1994) Angiotensin converting enzyme insertion/deletion polymorphism: association with ethnic origin. J Hypertens 12: 955–957
Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charm A, Tiret L, Cambien F, Corvol P, Soubrier F (1994) Angiotensin II type 1 receptor gene polymorphism in human essential hypertension. Hypertension 24: 63–69
Botero-velez M, Curtis JJ, Warnock DG (1994) Liddle’s syndrome revisited-A disorder of sodium reabsorption in the distal tubule. New Engl J Med 330: 178–181
Brunner HR, Laragh JH, Baer L (1972) Essential hypertension: renin and aldosterone heart attack and stroke. New Engl J Med 286: 441–449
Cambien F, Alhenc-Gelas F, Herbeth B, André JL, Rakotovao R, Gonzales MF, Allegrini J, Bloch C (1988) Familial resemblance of plasma angiotensin converting enzyme levels. Am J Human Genet 43: 774–780
Cambien F, Poirier O, Lecert L, Evans A, Cambou JP, Arveller D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359: 641–644
Caulfield M, Lavender P, Farrall M, Munroe P, Lawson M, Turner P, Clark AJL (1994) Linkage of the angiotensinogen gene to essential hypertension. New Engl J Med 330: 1629–1633
Cohen-Haguenauer O, Soubrier F, N’Guyene VC, Serero S, Turleau C, Jegou C, Gross MS, Corvol P, Frezal J (1983) Regional mapping of the human renin gene to 1q32 by in situ hybridization. Ann Genet (Paris) 32: 16–20
Cooper DW, Hill JA, Chesley LC (1988) Genetic control of susceptibility to eclampsia and miscarriage. Br J Obstet Gynecol 95: 644
Costerousse O, Allegrini J, Lopez M, Alhenc-Gelas F (1993) Angiotensin I-converting enzyme in human circulating mononuclear cells. Genetic polymorphism of expression in T-lymphocytes. Biochem J 290: 33–40
Curnow K, Pascoe L, White PC (1992) Genetic analysis of the human type-1 angiotensin II receptor. Mol Endocrinol 6: 1113–1118
Doira A, Warram JH, Krolewski AS (1994) Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I-converting enzyme gene. Diabetes 43: 690–694
Duru K, Farrow S, Wang JM, Lockette W, Kurtz T (1994) Frequency of a deletion polymorphism in the gene for angiotensin converting enzyme is increased in African-Americans with hypertension. Am J Hypertens 7: 759–762
Fasola AF, Martz BL, Helmer OM (1968) Plasma renin activity during supine exercise in offsprings of hypertensive parents. J Appl Physiol 25: 410–415
Furuta H, Deng-Fu G, Inagami T (1992) Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor. Biochem Biophys Res Commun 183: 8–13
Gaillard I, Clauser E, Corvol P (1989) Structure of human angiotensinogen gene DNA 8: 87–89
Gaillard-Sanchez I, Mattei MG, Clauser E, Corvol P (1990) Assignment by in situ hybridization of angiotensinogen to chromosome band 1q42: the same region as human renin gene. Human Genet 84: 341–343
Harrap SB, Davidson RH, Connor MJ, Soubrier F, Corvol P, Fraser R, Foy CJW, Watt GCM (1993) The angiotensin I converting enzyme gene polymorphism, predisposition to high blood pressure and activity of the renin-angiotensin system. Hypertension 21: 455–460
Hata A, Namikawa C, Saski M, Sato K, Nakamura T, Tamura K (1994) Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest 93: 1285–1287
Hegile RA, Brunt H, Connelly PW (1994) A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate. Circulation 90: 2207–2212
Higashimori K, Zhao Y, Higaki J, Kamitani A, Katsuya A, Nakuyra J, Miki T, Mikami H, Ogihara T (1993) Association of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population. Biochem Biophys Res Commun 191: 393–404
Hibert P, Lindpaintner K, Beckmann JS, Serikawa T, Soubrier F, Dubay C, Cartwright P, De Gouyon B, Julier C, Takahasi S, Vincent M, Ganten D, Georges M, Lathrop GM (1991) Chromosomal mapping of two genetic loci associated with blood pressure regulation in hereditary hypertensive rats. Nature 353: 521–526
Howard TE, Shai SY, Langford KG, Martin BM, Bernstein KE (1990) Transcription of testicular angiotensin-converting enzyme (ACE) is initiated within the 12th intron of the somatic ACE gene. Mol Cell Biol 10: 4294–4302
Hubert C, Houot AM, Corvol P, Soubrier F (1991) Structure of the angiotensin I-converting enzyme gene: two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 266: 15377–15383
Ishigami T, Iwamoto T, Tamura K, Yagamuchi S, Iwasawa K, Uchino K, Umemura S, Ishii M (1995) Angiotensin I converting enzyme (ACE) gene polymorphism and essential hypertension in Japan. Ethnic difference of ACE genotype. Am J Hypertens 8: 95–97
Iwai N, Ohmichi N, Nakamura Y, Mitsunnami X, Kinoshita M (1994) Molecular variants of the angiotensinogen gene and hypertension in a Japanese population. Hypertens Res 17: 117–121
Jacob HJ, Lindpaintner K, Lincoln SE, Kusumi K, Bunker RK, Mao YP, Ganten D, Dzau VJ, Lander ES (1991) Genetic mapping of a gene causing hypertension in the stroke prone spontaneously hypertensive rat. Cell 67: 213–224
Jeunemaitre X, Rigat B, Charm A, Houot AM, Soubrier F, Corvol P (1992a) Sib pair linkage analysis of renin gene haplotypes in human essential hypertension. Human Genet 88: 301–306
Jeunemaitre X, Lifton RP, Hunt SC, Williams RR, Lalouel JM (1992b) Absence of linkage between the angiotensin-converting enzyme locus and human essential hypertension. Nature Genet 1: 72–75
Jeunemaitre X, Soubrier F, Kotelevtsev Y, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel J-M, Corvol P (1992c) Molecular basis of human hypertension. Role of angiotensinogen. Cell 71: 169–180
Jeunemaitre X, Charru A, Chatellier G, Dumont C, Sassano P, Soubrier F, Mènard J, Corvol P (1993) M235T variant of the human angiotensinogen gene in unselected hypertensive patients. J Hypertens 11 (Suppl 5): S80–S81
Kamitani A, Rakugi H, Higaki J, Yi Z, Miki T, Ogihara T (1994) Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese. J Human Hypertens 8: 521–524
Kotelevstev YV, Clauser E, Corvol P, Soubrier F (1991) Dinucleotides repeat polymorphism in the human angiotensinogene gene. Nucl Acids Res 19: 6978
Kumar RS, Thekkumkara TJ, Sen GC (1991) The mRNAs encoding the two angiotensin-converting isozymes are transcribed from the same gene by a tissue-specific choice of alternative transcription initiation sites. J Biol Chem 266: 3854–3862
Lee EJD (1994) Population genetics of the angiotensin-converting enzyme in Chinese. Br J Clin Pharmacol 37: 212–214
Liddle GW, Bledsoe T, Coppage WS (1963) A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Physicians 76: 199–213
Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel JM (1992) A chimaeric 11ß-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 355: 262–265
Liston WA, Kilpatrick DC (1991) Is genetic susceptibility to pre-eclampsia conferred by homozygosity for the same single recessive gene in mother and fetus? J Obstet Gynecol 98: 1079–1086
Marian AJ, Yu QT, Workman R, Greeve G, Roberts R (1993) Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. Lancet 342: 1085–1086
Marre M, Bernadet P, Gallois Y, Savagner F, Guyene TT, Hallab M, Cambien F, Passa P, Alhenc-Gelas F (1994) Relationship between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 43: 384–388
Mattei MG, Hubert C, Alhenc-Gelas F, Rolckel N, Corvol P, Soubrier F (1989) Angiotensin I converting enzyme is on chromosome 17. 10th International Workshop on Human Gene Mapping, New Haven, Connecticut, June 11–17, 1989. Cytogenet Cell Genet 51: 1041
Meade TW, Cooper JA, Peart WS (1993) Plasma renin activity and ischemic heart disease. New Engl J Med 329: 619
Morris BJ, Griffiths LR (1988) Frequency in hypertensives of alleles for a RELP associated with the renin gene. Biochem Biophys Res Commun 150: 219–224
Morris BJ, Zee RYL, Schrader AP (1994) Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals. J Clin Invest 94: 1085–1089
Mullins JJ, Peters J, Ganten D (1990) Fulminant hypertension in rats harboring the mouse Ren 2 gene. Nature 344: 541–544
Naftilan AJ, Williams R, Burt D, Paul M, Pratt RE, Hobart P, Chirgwin J, Dzau VJ (1989) A lack of linkage of renin gene restriction length polymorphisms with human hypertension. Hypertension 14: 614–618
Otishi M, Fujii K, Minaminot T, Higaki J, Kamitani A, Rakugi H, Zhao Y, Hikami H, Miki T, Ogihara T (1993) A potent genetic risk factor for restenosis. Nature Genet 5: 324–325
Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, Dumon J, Vassart G (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365: 649–651
Pascoe L, Curnow KM, Slutsker L, Connell JMC, Speiser PW, New MI, White P (1992) Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2. Proc Natl Acad Sci USA 89: 8327–8331
Rapp JP, Wang SH, Dene H (1989) A genetic polymorphism in the renin gene of Dahl rats cosegregates with blood pressure. Science 243: 542–544
Raynolds MC, Bristow MR, Bush EW, Abraham WT, Lowes BD, Zisman LS, Taft CS, Perryman MB (1993) Angiotensin-Converting enzyme DD genotype in patients with ischaemic or dilated cardiomyopathy. Lancet 342: 1073–1075
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86: 1343–1346
Rotoimi C, Morrison L, Cooper R, Oyejide C, Effiong E, Lapids M, Osotemihen B, Ward R (1994) Angiotensinogen gene in human hypertension: Lack of an association of 235T allele among African Americans. Hypertension 24: 591–594
Ruiz J, Blanché H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P (1994) Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 91: 3662–3665
Schmidt S, Van Hoof IMS, Grobbee DE, Ganten D, Ritz E (1993) Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: Dutch hypertension and offspring study. J Hypertension 11: 345–348
Schunkert H, Hense H-W, Holmer SR, Stender M, Perz S, Keil U, Lorell BH, Riegger GA (1994) Association between a deletion polymorphism of the angiotensin-converting enzyme gene and left ventricular hypertrophy. New Engl J Med 330: 1634–1638
Shenker A, Laue L, Kasugi S, Merendino JJ, Minegishi T, Cutler GB (1993) A constitutively active mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 365: 652–654
Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR, Ulick S, Milora RV, Findling JW, Canessa C, Rossier BC, Lifton RP (1994) Liddle’s syndrome: Heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channel. Cell 79: 407–414
Soubrier F, Alhenc-Gelas F, Hubert C, Allegrini J, John M, Tregar G, Corvol P (1988) Two putative active centers in human angiotensin I converting enzyme revealed by molecular cloning. Proc Natl Acad Sci (USA) 85: 9386–9390
Soubrier F, Jeunemaitre X, Rigat B, Houot AM, Cambien F, Corvol P (1990) Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects. Hypertension 16: 712–717
Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F (1992) Evidence from combined segregation and linkage analysis that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Human Genet 51: 197–210
Tiret L, Kee F, Poirier 0, Micaud V, Lecerf L, Evans A, Cambon JP, Arveiler D, Luc G, Amoyel P, Cambien F (1993) Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction. Lancet 341: 991–993
Tiret L, Bonnardeaux A, Poirier 0, Ricard S, Marques-Vidal P, Evans A, Arveiler D, Luc G, Kee F, Ducimetierre P, Soubrier F, Cambien F (1994) Synergistic effects of angiotensin converting enzyme and angiotensin II type 1 receptor gene polymorphisms on risk of myocardial infarction. Lancet 344: 910–913
Volpe M, Lembo G, De Luca N, Lamenza F, Tritto C, Ricciaderli B, Molaro M, De Campera P, Condorelli G, Rendina V, Trimarco B, Condorelli M (1991) Abnormal hormonal and renal responses to saline load in hypertensive patients with parental history of cardiovascular accidents. Circulation 84: 92–100
Walker WG, Whelton PK, Saito H, Russel R, Hermann J (1979) Relation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects. Hypertension 1: 287–291
Ward R (1990) Familial aggregation and genetic epidemiology of blood pressure. In: Laragh JH, Brenner BM (eds), Hypertension: pathophysiology, diagnosis and management. Raven Press, New York, pp 81–100
Ward K, Hata PF, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S, Berrebi S, Sasaki M, Corvol P, Lifton R, Lalouel JM (1993) A molecular variant of angiotensinogen associated with preeclampsia. Nature Genet 4: 59–61
Watt GCM, Harrap SB, Foy CJW, Holton DW, Edwards HV, Davidson R, Connor JM, Lever AF, Fraser R (1992) Abnormalities of glucocorticoid metabolism and the renin angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure. J Hypertension 10: 473–482
Zee RYL, Lou YK, Griffiths LR, Morris BJ (1992) Association of an insertion/deletion polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 184: 9–15
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Corvol, P., Soubrier, F., Jeunemaitre, X. (1996). Molecular Genetics of the Renin Angiotensin Aldosterone System in Human Hypertension. In: Berg, K., Boulyjenkov, V., Christen, Y. (eds) Genetic Approaches to Noncommunicable Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61028-8_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-61028-8_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64662-1
Online ISBN: 978-3-642-61028-8
eBook Packages: Springer Book Archive