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The Genetic Basis of Essential Hypertension and Its Implications for Treatment

  • Chapter
Cardiovascular Pharmacogenetics

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 160))

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Abstract

Hypertension is an asymptomatic condition but a major risk factor for cardiovascular events and stroke. Blood pressure exhibits a skewed normal distribution in the general population with no natural hypertensive threshold. Decisions regarding who to treat and with what drugs are based upon morbidity and mortality data in large population studies, the presence/absence of co-existing disease and cost. Because of variation between individuals in their response to antihypertensive drugs, patients are frequently exposed to a number of different drugs before a suitable agent (or combination of agents) is found. This increases the potential for adverse drug reactions and/or poor compliance. A few patient characteristics can be used to help predict their blood pressure response to a drug such as age, race and perhaps renin levels. Genetic factors also influence the level of blood pressure in an individual, susceptibility to target organ damage and the response to antihypertensive drugs. Genes with a large influence on blood pressure have been identified for rare familial forms of hypertension, but these account for a very small fraction of the general hypertensive population. Their elucidation has helped define pathophysiological pathways and suggests new biochemical factors for further genetic studies or drug targeting. The hunt is on for genes which influence blood pressure in a much larger proportion of the population. The broader vision is that knowledge of a patient’s genotype coupled with epidemiological and clinical data can help in tailoring therapy to the individual patient. How useful it turns out to be will ultimately depend upon whether blood pressure is regulated by a relatively small number of genes with significant effects or a large number of genes with very small effects.

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References

  • Aitman TJ, Glazier AM, Wallace CA et al (1999)Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats [see comments]. Nat Genet 21: 76–83

    Google Scholar 

  • Altmuller J, Palmer LJ, Fischer G et al (2001) Genomewide scans of complex human diseases: true linkage is hard to find. Am J Hum Genet 69: 936–950

    Article  PubMed  CAS  Google Scholar 

  • Altshuler D, Hirschhorn JN, Klannemark M et al (2000) The common PPARgamma Prol2Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26: 76–80

    Article  PubMed  CAS  Google Scholar 

  • Anonymous (1999) Freely associating. Nat Genet 22 (1): 1–2

    Article  CAS  Google Scholar 

  • Arnett DK, Boerwinkle E, Davis BR et al (2002) Pharmacogentic Approaches to hypertension therapy: design and rationale for the Genetic of Hypertension Associated Treatment ( GenHAT) study. The Pharmacogenetics J 2: 309–317

    Google Scholar 

  • Arngrimsson R, Hayward C, Nadaud S et al (1997) Evidence for a familial pregnancy-in- duced hypertension locus in the eNOS-gene region. Am J Hum Genet 61: 354–362

    Article  PubMed  CAS  Google Scholar 

  • Arngrimsson R, Sigurard TS, Frigge ML et al (1999) A genone-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13. Hum Mol Genet 8: 1799–1805

    Article  PubMed  CAS  Google Scholar 

  • Baker EH, Dong YB, Sagnella GA et al (1998) Association of hypertension with T594 M mutation in beta subunit of epithelial sodium channels in black people resident in London. Lancet 351: 1388–1392

    Article  PubMed  CAS  Google Scholar 

  • Baker EH, Duggal A, Dong Y et al (2002) Amiloride, a specific drug for hypertension in black people with T594 M variant? Hypertension 40: 13–17

    Article  PubMed  CAS  Google Scholar 

  • Benjafield AV, Jeyasingam CL, Nyholt DR et al (1998) G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension. Hypertension 32: 1094–1097

    Article  PubMed  CAS  Google Scholar 

  • Bergman S, Key BO, Kirk KA et al (1996) Kidney disease in the first-degree relatives of African-Americans with hypertensive end-stage renal disease. Am J Kidney Dis 27: 341–346

    Article  PubMed  CAS  Google Scholar 

  • Bianchi G, Tripodi G, Casari G et al (1994) Two point mutations within the adducin genes are involved in blood pressure variation. Proc Natl Acad Sci U S A 91: 3999–4003

    Article  PubMed  CAS  Google Scholar 

  • Bonnardeaux A, Nadaud S, Charru A et al (1995) Lack of evidence for linkage of the endothelial cell nitric oxide synthase gene to essential hypertension. Circulation 91: 96–102

    Article  PubMed  CAS  Google Scholar 

  • Bray MS, Krushkal J, Li L et al (2000) Positional genomic analysis identifies the beta(2)adrenergic receptor gene as a susceptibility locus for human hypertension. Circulation 101: 2877–2882

    Article  PubMed  CAS  Google Scholar 

  • Bray MS, Li L, Turner ST et al (2000) Association and linkage analysis of the alpha-adducin gene and blood pressure. Am J Hypertens 13: 699–703

    Article  PubMed  CAS  Google Scholar 

  • Brown DM, Provoost AP, Daly MJ et al (1996) Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat. Nat Genet 12: 44–51

    Article  PubMed  CAS  Google Scholar 

  • Caulfield M, Lavender P, Farrall M et al (1994) Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 330: 1629–1633

    Article  PubMed  CAS  Google Scholar 

  • Caulfield M, Lavender P, Newell-Price J et al (1995) Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest 96: 687–692

    Article  PubMed  CAS  Google Scholar 

  • Caulfield M, Pembroke J, Dominiczak A et al (2002) The MRC British Genetics of Hypertension Study: genome-wide results. J Hum Hypertens 2002; 16: 896

    Google Scholar 

  • Collison M, Glazier AM, Graham D et al (2000) Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat. Diabetes 49: 2222–2226

    Article  PubMed  CAS  Google Scholar 

  • Corvol P, Persu A, Gimenez-Roqueplo AP et al (1999) Seven lessons from two candidate genes in human essential hypertension: angiotensinogen and epithelial sodium channel. Hypertension 33: 1324–1331

    Article  PubMed  CAS  Google Scholar 

  • Cowley AW, Jr., Roman RJ, Kaldunski ML et al (2001) Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat. Hypertension 37: 456–461

    Article  PubMed  CAS  Google Scholar 

  • Cui Y, Su YR, Rutkowski M et al (1997) Loss of protein kinase C inhibition in the beta-T594 M variant of the amiloride-sensitive Na+ channel. Proc Natl Acad Sci USA 94: 9962–9966

    Article  PubMed  CAS  Google Scholar 

  • Cusi D, Barlassina C, Azzani T et al (1997) Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet 349: 1353–1357

    Article  PubMed  CAS  Google Scholar 

  • Cvetkovic B, Keen HL, Zhang X et al (2002) Physiological significance of two common haplotypes of human angiotensinogen using gene targeting in the mouse. Physiol Genomics

    Google Scholar 

  • Dahlman I, Eaves IA, Kosoy R et al. (2002) Parameters for reliable results in genetic association studies in common disease. Nat Genet 30: 149–150

    Article  PubMed  CAS  Google Scholar 

  • DeStefano AL, Baldwin CT, Burzstyn M et al. (1998) Autosomal dominant orthostatic hypotensive disorder maps to chromosome 18q. Am J Hum Genet 63: 1425–1430

    Article  PubMed  CAS  Google Scholar 

  • Dominiczak AF, Negrin DC, Clark JS et al (2000). Genes and hypertension: from gene mapping in experimental models to vascular gene transfer strategies. Hypertension 35: 164–172

    Article  PubMed  CAS  Google Scholar 

  • Eaves IA, Merriman TR, Barber RA et al (2000) The genetically isolated populations of Finland and Sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes. Nat Genet 25: 320–323.

    Article  PubMed  CAS  Google Scholar 

  • Ferrandi M, Salardi S, Tripodi G et al. (1999) Evidence for an interaction between adducin and Na(+)-K(+)-ATPase: relation to genetic hypertension. Am J Physiol 277: H1338 - H1349

    PubMed  CAS  Google Scholar 

  • Fornage M, Amos CI, Kardia S et al (1998) Variation in the region of the angiotensin-converting enzyme gene influences interindividual differences in blood pressure levels in young Caucasian males. Circulation 97: 1773–1779

    Article  PubMed  CAS  Google Scholar 

  • Freedman BI, Rich SS, Yu Hongrun et al (2002) Linkage heterogeneity of end-stage renal disease on human chromosome 10. Kidney Internat 62: 770–774

    Article  CAS  Google Scholar 

  • Glorioso N, Manunta P, Filigheddu F et al (1999) The role of alpha-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study. Hypertension 34: 649–654

    Article  PubMed  CAS  Google Scholar 

  • Hasson A, Lansbury A, Catto AJ et al (2002) Angiotensin converting enzyme insertion/ deletion genotype is associated with leukoaraiosis in lacunar syndromes. J Neurol Neurosurg Psychiatry 72: 343–346

    Article  Google Scholar 

  • Hata A, Namikawa C, Sasaki M et al (1994) Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest 93: 1285–1287

    Article  PubMed  CAS  Google Scholar 

  • Hegele RA, Anderson C, Young TK et al (1999) G-protein beta3 subunit gene splice variant and body fat distribution in Nunavut Inuit. Genome Res 9: 972–977

    Article  PubMed  CAS  Google Scholar 

  • Hegele RA, Brunt JH, Connelly PW (1994) A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate. Circulation 90: 2207–2212

    Article  PubMed  CAS  Google Scholar 

  • Hegele RA, Harris SB, Hanley AJ et al (1998) -6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree. J Hum Genet 43: 37–41

    Google Scholar 

  • Huang PL, Huang Z, Mashimo H et al (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377: 239–242

    Article  PubMed  CAS  Google Scholar 

  • Hunt SC, Ellison RC, Atwood I,D et al (2002) Genome scans for blood pressure and hypertension: the National Heart, Lung, and Blood Institute Family Heart Study. Hypertension 40: 1–6

    Google Scholar 

  • Hyndman ME, Parsons HG, Verma S et al (2002) The T-786->C mutation in endothelial nitric oxide synthase is associated with hypertension. Hypertension 39: 919–922

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa K, Imai Y, Katsuya T et al (2000) Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure. Am J Hypertens 13: 140–145

    Article  PubMed  CAS  Google Scholar 

  • Jacob HJ, Lindpaintner K, Lincoln SE et al (1991)Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67: 213–224

    Google Scholar 

  • Jeerooburkhan N, Jones LC, Bujac S et al (2001) Genetic and environmental determinants of plasma nitrogen oxides and risk of ischemic heart disease. Hypertension 38: 1054–1061

    Article  PubMed  CAS  Google Scholar 

  • Jeffs B, Clark JS, Anderson NH et al (1997) Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus. Nat Genet 16: 364–367

    Article  PubMed  CAS  Google Scholar 

  • Jeffs B, Negrin CD, Graham D et al (2000) Applicability of a “speed” congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. Hypertension 35: 179–187.

    Article  PubMed  CAS  Google Scholar 

  • Jeunemaitre X, Lifton RP, Hunt SC et al (1992) Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nat Genet 1: 72–75

    Article  PubMed  CAS  Google Scholar 

  • Jeunemaitre X, Soubrier F, Kotelevtsev YV et al (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71: 169–180

    Article  PubMed  CAS  Google Scholar 

  • Kajiyama N, Saito Y, Miyamoto Yet al (2000) Lack of association between T-786->C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene and essential hypertension. Hypertens Res 23: 561–565

    Article  PubMed  CAS  Google Scholar 

  • Karet F (2003) Monogenic tubular salt and acid transporter disorders. J Nephrol 15 [Suppl 6]: S57 - S68

    Google Scholar 

  • Kato N, Sugiyama T, Morita H et al (1999) Angiotensinogen gene and essential hypertension in the Japanese: extensive association study and meta-analysis on six reported studies. J Hypertens 17: 757–763

    Article  PubMed  CAS  Google Scholar 

  • Khono M, Yokokawa K, Minami M et al (1999) Association between angiotensin-converting enzyme gene polymorphisms and regression of left ventricular hypertrophy in patients treated with angiotensin-converting enzyme inhibitors. Am J Med 106; 544549.

    Google Scholar 

  • Klag MJ, Whelton PK, Randall BL et al (1997) End-stage renal disease in African-Ameri- can and Caucasian men. 16-year MRFIT findings. J Am Med Assoc 277: 1293–1298

    Article  CAS  Google Scholar 

  • Kostulas K, Huang W-X, Crisby M et al (1999) An angiotensin-converting enzyme gene polymorphism suggests a genetic distrinction between ischaemic stroke and carotid stenosis. Eur J Clin Invest 29: 478–483

    Article  PubMed  CAS  Google Scholar 

  • Kristjansson K, Manolescu A, Kristinsson A et al (2002) Linkage of essential hypertension to chromosome 18q. Hypertension 39: 1044–1049

    Article  PubMed  CAS  Google Scholar 

  • Krushkal J, Ferrell R, Mockrin SC et al (1999) Genome-wide linkage analyses of systolic blood pressure using highly discordant siblings. Circulation 9: 1407–1410

    Article  Google Scholar 

  • Lander ES, Botstein D (1989) Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121: 185–199

    PubMed  CAS  Google Scholar 

  • Levy D, DeStefano AL, Larson MG et al (2000) Evidence for a gene influencing blood pressure on chromosome 17. Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the framingham heart study. Hypertension 36: 477–483

    Google Scholar 

  • Liggett SB (1997) Polymorphisms of the beta2-adrenergic receptor and asthma. Am J Respir Crit Care Med 156: S156 - S162

    PubMed  CAS  Google Scholar 

  • Mackay TF (2001) The genetic architecture of quantitative traits. Annu Rev Genet 35: 303–339

    Article  PubMed  CAS  Google Scholar 

  • Matsubara M, Metoki H, Suzuki M et al (2002) Genotypes of the betaENaC gene have little influence on blood pressure level in the Japanese population. Am J Hypertens 15: 189–192

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto Y, Saito Y, Kajiyama N et al (1998) Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 32: 3–8

    Article  PubMed  CAS  Google Scholar 

  • Myerson SG, Montgomery HE, Whittingham M et al (2001) Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomised controlled trial with losartan. Circulation 103: 226–230

    Article  PubMed  CAS  Google Scholar 

  • Nadeau JH, Frankel WN (2000) The roads from phenotypic variation to gene discovery: mutagenesis versus QTLs. Nat Genet 25: 381–384

    Article  PubMed  CAS  Google Scholar 

  • Nadeau JH, Singer JB, Matin A et al (2000) Analysing complex genetic traits with chromosome substitution strains. Nat Genet 24: 221–225

    Article  PubMed  CAS  Google Scholar 

  • Negrin CD, McBride MW, Carswell HV et al (2001) Reciprocal consomic strains to evaluate y chromosome effects. Hypertension 37: 391–397

    Article  PubMed  CAS  Google Scholar 

  • Nickerson DA, Taylor SL, Weiss KM et al (1998) DNA sequence diversity in the 9.7-kb region of the human lipoprotein lipase gene. Nat Genet 19: 233–240

    Article  PubMed  CAS  Google Scholar 

  • Niu T, Chen C, Yang J et al (1999) Blood pressure and the T174 M and M235T polymorphisms of the angiotensinogen gene. Ann Epidemiol 9: 245–253

    Article  PubMed  CAS  Google Scholar 

  • Niu T, Xu X, Cordell HJ et al (1999) Linkage analysis of candidate genes and gene-gene interactions in chinese hypertensive sib pairs. Hypertension 33: 1332–1337

    Article  PubMed  CAS  Google Scholar 

  • Niu T, Yang J, Wang B et al (1999) Angiotensinogen gene polymorphisms M235T/ T174 M: no excess transmission to hypertensive Chinese. Hypertension 33: 698–702

    Article  PubMed  CAS  Google Scholar 

  • Nothnagel M, Ott J (2002) Statistical gene mapping of traits in humans-hypertension as a complex trait: is it amenable to genetic analysis? Semin Nephrol 22: 105–114

    Article  PubMed  CAS  Google Scholar 

  • O’Donnell CJ, Lindpaintner K, Larson MG et al (1998) 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 97: 1766–1772

    Article  PubMed  Google Scholar 

  • Persu A, Barbry P, Bassilana F et al (1998) Genetic analysis of the beta subunit of the epithelial Na+ channel in essential hypertension. Hypertension 32: 129–137

    Article  PubMed  CAS  Google Scholar 

  • Pravenec M, Zidek V, Simakova M et al (1999) Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. J Clin Invest 103: 1651–1657

    Article  PubMed  CAS  Google Scholar 

  • Price DA, Crook ED (2002) Kidney disease in African Americans: genetic considerations. J Natl Med Assoc 94 (8 Suppl): 16S - 27S

    PubMed  Google Scholar 

  • Province MA, Boerwinkle E, Chakravarti A et al (2000) Lack of association of the angiotensinogen-6 polymorphism with blood pressure levels in the comprehensive NHLBI Family Blood Pressure Program. National Heart, Lung and Blood Institute. J Hyper-tens 18: 867–876

    Google Scholar 

  • Province MA, Kardia SLR, Ranade K et al (2003) A Meta-Analysis of Genome-Wide Linkage Scans for Hypertension:The National Heart,Lung and Blood Institute Family Blood Pressure Program. Am J Hypertens 16: 144–147

    Article  PubMed  Google Scholar 

  • Ranade K, Hsuing AC, Wu KD et al (2000) Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations. Am J Hypertens 13: 704–709

    Article  PubMed  CAS  Google Scholar 

  • Rapp JP (2000) Genetic analysis of inherited hypertension in the rat. Physiol Rev 80: 135–172

    PubMed  CAS  Google Scholar 

  • Rapp JP, Garrett MR, Deng AY (1998) Construction of a double congenic strain to prove an epistatic interaction on blood pressure between rat chromosomes 2 and 10. J Clin Invest 101: 1591–1595

    Article  PubMed  CAS  Google Scholar 

  • Reich DE, Schaffner SF, Daly MJ et al(2002) Human genome sequence variation and the influence of gene history, mutation and recombination. Nat Genet 32: 135–142

    Google Scholar 

  • Rice T, Rankinen T, Province MA et al (2000) Genome-wide linkage analysis of systolic and diastolic blood pressure: the Quebec Family Study. Circulation 102: 1956–1963

    Article  PubMed  CAS  Google Scholar 

  • Rieder MJ, Taylor SL, Clark AG et al (1999) Sequence variation in the human angiotensin converting enzyme. Nat Genet 22: 59–62

    Article  PubMed  CAS  Google Scholar 

  • Rigat B, Hubert C, Alhenc-Gelas F et al (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

    Article  PubMed  CAS  Google Scholar 

  • Rubattu S, Lee-Kirsch MA, dePaolis P et al (1999) Altered structure, regulation, and function of the gene encoding the atrial natriuretic peptide in the stroke-prone spontaneously hypertensive rat. Circ Res 85: 900–905

    Article  PubMed  CAS  Google Scholar 

  • Sasaki M, Oki T, Luchi A et al (1996) 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 14: 1403–1408

    Google Scholar 

  • Schork NJ, Chakravarti A, Thiel B et al (2000) Lack of association between a biallelic polymorphism in the adducin gene and blood pressure in Caucasians and African Americans. Am J Hypertens 13: 693–698.

    Article  PubMed  CAS  Google Scholar 

  • Schunkert H, Hense HW, Doring A et al (1998) Association between a polymorphism in the G protein beta3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension 32: 510–513

    Article  PubMed  CAS  Google Scholar 

  • Seino Y, Ikeda U, Maeda Y et al (1998) Angiotensin-converting enzyme gene polymorphism and plasminogen activator inhibitor 1 levels in subjects with cerebral infarction. J Thrombosis and Throbolysis 5: 263–267

    Article  CAS  Google Scholar 

  • Sierra C, Coca A, Gomez-Angelats E et al (2002) Renin-angiotensin system genetic polymorphisms and cerebral white matter lesions in essential hypertension. Hypertension 39: 343–347.

    Article  PubMed  CAS  Google Scholar 

  • Siffert W, Forster P, Jockel KH et al (1999) 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 10: 1921–1930

    Google Scholar 

  • Siffert W, Rosskopf D, Moritz A et al (1995) Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Clin Invest 96: 759766

    Google Scholar 

  • Siffert W, Rosskopf D, Siffert G et al (1998) Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet 18: 45–48

    Article  PubMed  CAS  Google Scholar 

  • Stephens JC, Schneider JA, Tanguay DA et al (2001) Haplotype Variation and Linkage Disequilibrium in 313 Human Genes. Science 293: 489–493

    Article  PubMed  CAS  Google Scholar 

  • Stoll M, Jacob HJ. (2001) Genetic rat models of hypertension: relationship to human hypertension. Curr Hypertens Rep 3: 157–164

    Article  PubMed  CAS  Google Scholar 

  • Stoll M, Kwitek-Black AE, Cowley AW et al (2000) New target regions for human hypertension via comparative genomics. Genome Res 10: 473–482

    Article  PubMed  CAS  Google Scholar 

  • Sugiyama F, Churchill GA, Higgins DC et al (2001) Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci. Genomics 71: 70–77

    Article  PubMed  CAS  Google Scholar 

  • Takami S, Imai Y, Katsuya T et al (2000) Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction. The Ohasama Study. Am J Hypertension 13: 121–127

    Google Scholar 

  • Takami S, Wong ZY, Stebbing M et al (1999) Linkage analysis of endothelial nitric oxide synthase gene with human blood pressure. J Hypertens 17: 1431–1436

    Article  PubMed  CAS  Google Scholar 

  • Tesauro M, Thompson WC, Rogliani P et al (2000) Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A 97: 2832–2835

    Article  PubMed  CAS  Google Scholar 

  • The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group (2002) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288: 3039–3042

    Article  Google Scholar 

  • Province MA, Kardia SLR, Ranade K et al (2003). A meta-analysis of genome-wide linkage scans for hypertension:The National Heart, Lung and Blood Institute Family Blood Pressure Program. Am J Hypertens 16: 144–147.

    Google Scholar 

  • Tiago AD, Nkeh B, Candy GP et al (2001) Association study of eight candidate genes with renin status in mild-to-moderate hypertension in patients of African ancestry. Cardiovasc J S Afr 12: 75–80

    PubMed  CAS  Google Scholar 

  • Tiret L, Poirier O, Nicaud V et al (2002) Heterogeneity of linkage disequilibrium in human genes has implications for association studies of common diseases. Hum Mol Genet 11: 419–429

    Article  PubMed  CAS  Google Scholar 

  • Tomaszewski M, Brain NJ, Charchar FJ et al (2002) Essential hypertension and beta2-adrenergic receptor gene: linkage and association analysis. Hypertension 40: 286–291

    Article  PubMed  CAS  Google Scholar 

  • Tournier-Lasserve E (2002) New players in the genetics of stroke. N Engl J Med 347: 1711–1712

    Article  PubMed  Google Scholar 

  • Turner ST, Boerwinkle E (2000) Genetics of hypertension, target-organ complications, and response to therapy. Circulation 102:IV40–IV45

    Google Scholar 

  • Turner ST, Boerwinkle E, Sing CF (1999) Context-dependent associations of the ACE I/D polymorphism with blood pressure. Hypertension 34: 773–778

    Article  PubMed  CAS  Google Scholar 

  • Wayne ML, McIntyre LM (2002) Combining mapping and arraying: An approach to candidate gene identification. Proc Natl Acad Sci U S A 99: 14903–14906

    Google Scholar 

  • Wilson FH, Disse-Nicodeme S, Choate KA et al (2001) Human Hypertension Caused by Mutations in WNK Kinases. Science 293: 1107–1112

    Article  PubMed  CAS  Google Scholar 

  • Wilson FH, Kahle KT, Sabath E et al (2002) Molecular pathogenesis of inherited hypertension with hyperkalemia: The Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc Natl Acad Sci 100: 680–684

    Article  CAS  Google Scholar 

  • Winkelmann BR, Russ AP, Nauck M et al (1999) Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. Am Heart J 137: 698–705

    Article  PubMed  CAS  Google Scholar 

  • Wright FA, O’Connor DT, Roberts E et al. (1999) Genome Scan for Blood Pressure Loci in Mice. Hypertension 34: 625–630

    Article  PubMed  CAS  Google Scholar 

  • Wulff P, Vallon V, Huang DY et al (2002) Impaired renal Na+ retention in the sgkl-knockout mouse. J Clin Invest 110: 1263–1268

    PubMed  CAS  Google Scholar 

  • Xu X, Rogus JJ, Terwedow HA et al (1999) An extreme-sib-pair genome scan for genes regulating blood pressure. Am J Hum Genet 64: 1694–1701

    Article  PubMed  CAS  Google Scholar 

  • Zee RYL, Ridker PM, Stampfer MJ et al (1999) Prospective evaulation of the angiotensinconverting enzyme insertion/deletion polymorphism and the risk of stroke. Circulation 99: 340–343

    Article  PubMed  CAS  Google Scholar 

  • Zhu DL, Wang HY, Xiong MM et al (2001) Linkage of hypertension to chromosome 2g14-q23 in Chinese families. J Hypertens 19: 55–61

    Article  PubMed  CAS  Google Scholar 

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O’Shaughnessy, K.M., Wilkins, M.R. (2004). The Genetic Basis of Essential Hypertension and Its Implications for Treatment. In: Wilkins, M.R. (eds) Cardiovascular Pharmacogenetics. Handbook of Experimental Pharmacology, vol 160. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-06214-2_6

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