Pharmacogenomics of primary hypertension - The lessons from the past to look toward the future

Pharmacogenomics

Volumn 4, Issue 3, 2003, Pages 279-296

  Bianchi, Giuseppe ^a   Staessen, Jan A ^b   Patrizia, Ferrari ^c  

^a SAN RAFFAELE HOSPITAL   (Italy)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c Prassis Sigma Tau Research Institute   (Italy)

Author keywords

Blood pressure; Diuretic; Genotype; Pharmacogenomics; Primary hypertension

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ALDOSTERONE; ALDOSTERONE SYNTHASE; AMILORIDE; ANGIOTENSIN; ANGIOTENSIN II ANTAGONIST; ANGIOTENSIN RECEPTOR; ANGIOTENSINOGEN; ANTIHYPERTENSIVE AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM ANTAGONIST; CAPTOPRIL; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; HYDROCHLOROTHIAZIDE; INULIN; LISINOPRIL; MITOGEN ACTIVATED PROTEIN KINASE; OUABAIN; REACTIVE OXYGEN METABOLITE; RENIN; SODIUM; SPIRONOLACTONE; TUMOR NECROSIS FACTOR ALPHA;

AGE; ALLELE; CLINICAL STUDY; CLINICAL TRIAL; DRUG EFFICACY; DRUG RESPONSE; DRUG SELECTIVITY; ENVIRONMENTAL FACTOR; EXPERIMENTATION; GENDER; GENE FUNCTION; GENETIC ANALYSIS; GENOTYPE; GLOMERULUS FILTRATION RATE; HEALTH CARE COST; HUMAN; HYPERTENSION; KIDNEY ARTERY STENOSIS; LIDDLE SYNDROME; METHODOLOGY; NONHUMAN; PATHOPHYSIOLOGY; PHARMACOGENOMICS; POPULATION SIZE; PRIMARY HYPERALDOSTERONISM; PROGNOSIS; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIDE EFFECT; STATISTICAL ANALYSIS; TREATMENT PLANNING;

ANIMALS; ANTIHYPERTENSIVE AGENTS; GENOTYPE; HUMANS; HYPERTENSION; PHARMACOGENETICS;

GLOMERULUS; STROPHANTHUS GRATUS;

EID: 0038069290     PISSN: 14622416     EISSN: None     Source Type: Journal    
DOI: 10.1517/phgs.4.3.279.22694     Document Type: Review

References (195)

1. The Heart Outcomes Prevention Evaluation Study Investigators: Committee on the Conduct of Science National Academy of Sciences. On being a scientist. Proc. Natl. Acad. Sci. USA 86, 9053-9073 (1989).
2. The Heart Outcomes Prevention Evaluation Study Investigators: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N. Engl. J. Med. 342, 145-153 (2000).
3. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: Major cardiovascular events in hypertensive patients randomized to doxazosin versus chlorthalidone. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA 283, 1967-1975 (2000).
4. Staessen JA, Wang JIG, Thijs L: Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 358, 1305-1315 (2001).
5. The ALLAHAT Officers and Coordinators for the ALLAHT Collaborative Research Group Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blockers versus diuretic. JAMA 288, 2981-2997(2002).
6. Staessen JA, Wang J, Bianchi G, Birkenhäger WH: Essential hypertension (seminar). Lancet (2003) (In Press).
7. Progress Collaborative Group: Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 358, 1033-1041 (2001).
8. Zanchetti A, Ruilope LM: Antihypertensive treatment in patients with type-2 diabetes mellitus: what guidance from recent controlled randomized trials? J. Hypertens. 20, 2099-2110 (2002).
9. Prospective Studies Collaboration: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360, 1903-1913 (2002).
10. Mayer G: ACE genotype and ACE inhibitor response in kidney disease: a perspective. Am. J. Kidney Dis. 40(2), 227-235 (2002).
11. Dahlof B, Devereux RB, Kjeldensen SE et al.: Cardiovascular morbidity and mortality in the Losartan intervention for endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 359, 995-1003 (2002).
12. Weber MA: Unsolved problems in treating hypertension. Rationale for new approaches. Am. J. Hypertens. 11, 145S-149S (1998).
13. Berlowitz DR, Ash AA, Hichey EC et al.: Inadequate management of blood pressure in a hypertensive population. N. Engl. J. Med. 339, 1957-1963 (1998).
14. Banerjee D, Materson BJ: Blood pressure-independent impact of antihypertensive agents on cardiovascular and renal disease. Curr. Hypertens. Rep. 4, 445-452 (2002).
15. Miller JZ, Weinberger MH, Daugherty SA, Finebeg NS, Christian JC, Grim CE: Heterogeneity of blood pressure response to dietary sodium restriction in normotensive adults. J. Chronic Dis. 40(3), 245-250 (1987).
16. Hamet P. Pausova Z, Adarichev V, Adaricheva K, Tremblay J: Hypertension: genes and environment. J. Hypertens. 16, 397-418 (1998).
17. Lifton RP: Molecular genetics of human blood pressure variation. Science 272, 676-680 (1996).
18. Turner ST, Boerwinkle E: Genetics of blood pressure, hypertensive complications, and antihypertensive drug responses. Pharmacogenomics 4(1), 53-65 (2003).
19. Dudley C, Keavney B, Casadei B, Conway J, Bird R, Ratcliffe P: Prediction of patient responses to antihypertensive drugs using genetic polymorphism: investigation of renin-angiotensin system genes. J. Hypertens. 14, 259-262 (1996).
20. Sever P: The heterogeneity of hypertension: why doesn't every patient respond to every antihypertensive drug? J. Cardiovasc. Pharmacol. 31 (Suppl. 2), S1-S84 (1998).
21. Niutta E, Cusi D, Colombo R et al.: Predicting interindividual variation in anti-hypertensive therapy: the role of sodium transport systems and renin. J. Hypertens. 6(Suppl. 4), S53-S58 (1990).
22. Laragh JH, Lamport B, Sealey J, Alderman MH: Diagnosis ex juvantibus. Individual response patterns to drugs reveal hypertension mechanisms and simplify treatment. Hypertension 12, 223-226 (1988).
23. Menard J, Bellet M, Serrurier D: From the parallel group design to crossover design, and from the group approach to the individual approach. Am. J. Hypertens. 3(10), 815-819 (1990).
24. Bidiville J, Nussberger J, Wieber G, Porchet M, Waeber B, Brunner HR: Individual responses to converting enzyme inhibitors and calcium antagonists. Hypertension 11, 166-173 (1988).
25. Hofbauer KG, Huppertz C: Pharmacotherapy and evolution. Trends Ecol. Evol. 17(7), 328-334 (2002).
26. Lazzeroni LC, Karlovich CA: Genotype to phenotype: associations, errors and complexity. Trends Genet. 18(6), 283-284 (2002).
27. Schork NJ: Molecular genetics of hypertension. In: Genetics of Hypertension. Dominiczack AD, Connell, Soubrier (Eds), Bins SP Ltd, Oxford, 9-15 (1999).
28. Terwillinger JD, Goering HHH: Gene mapping in the 20th century and 21st centuries: statistical methods, data analysis and experimental design. Human Biol. 72, 63-132 (2000).
29. Barlassina C, Lanzani C, Manunta P, Bianchi G: Genetics of essential hypertension: from families to genes. J. Am. Soc. Nephrol. 13, S155-S164 (2002).
30. Bianchi G, Cusi D: Association and linkage analysis of α-adducin polymorphism: is the glass half full or half empty? Am. J. Hypertens. 13, 739-743 (2000).
31. Corvol P, Persu A, Gimenez-Roqueplo AP, Jeunemaitre X: Seven lessons from two candidate genes in human essential hypertension angiotensionogen and epithelial sodium channel. Hypertension 33, 1324-1331 (1999).
32. Niu T, Chen X, Xu X: Angiotensin converting enzyme gene insertion/deletion polymorphism and cardiovascular disease. Drugs 62(7), 977-993 (2002).
33. Luft FC: Molecular genetics of human hypertension. J. Hypertens. 16, 1871-1878 (1998).
34. Roses AD: Pharmacogenetics. Hum. Mol. Genet. 10(20), 2261-2267 (2001).
35. Cadman PE, O'Connor DT: Pharmacogenomics of hypertension. Curr. Opin. Nephrol. Hypertens. 12, 61-70 (2003).
36. Baudin B: Angiotensin II receptor polymorphisms in hypertension. Pharmacogenomic considerations. Pharmacogenomics 3(1), 65-73 (2002).
37. Samani NJ: Pharmacogenomics of hypertension: a realizable goal? Clin. Sci. 99, 231-232 (2000).
38. Hallberg P, Karlsson J, Kurland L et al.: The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA) trial. J. Hypertens. 20, 2089-2093 (2002).
39. Lifton RP. Dluhy RG: Inherited forms of mineralocorticoid hypertension: glucocorticoid-remediable aldosteronism and the syndrome of apparent mineralocorticoid excess. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 2) Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 2163-2175 (1995).
40. Shimkets RA, Warnock DG, Bositis CM et al.: Liddle's syndrome: heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channel. Cell 79, 407-414 (1994).
41. Gordon RD, Klemm SA, Tunny TJ, Stowasser M: Gordon's syndrome: a sodium-volume-dependent form of hypertension with a genetic bases. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 2). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 2111-2123 (1995).
42. Lifton RP Gharavi AG, Geller DS: Molecular mechanisms of human hypertension. Cell 104(40), 545-556 (2001).
43. Hall JE, Guyton AC, Brands MW. Control of sodium excretion and arterial pressure by intrarenal mechanisms and the renin-angiotensin system. In: Hypertension Pathophysiology Diagnosis, and Management (Vol. 1). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 1451-1475 (1995).
44. Hollenberg NK, Williams GH: Abnormal renal function, sodium-volume homeostasis and renin system behavior in normal-renin essential hypertension: devolution of the nonmodulator concept: In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 2) Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 1837-1856 (1995).
45. Klahr S, Morrissey J: Comparative effects of ACE inhibition and angiotensin II receptor blockade in the prevention of renal damage. Kidney Int. 62 (Suppl. 82), S23-S26 (2002).
46. Kohno M, Yokokawa K, Minami M et al.: 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(5), 544-549 (1999).
47. Baudin B: Angiotensin I-converting enzyme gene polymorphism and drug response. Clin. Chem. Lab. Med. 38(9), 853-856 (2000).
48. Turner ST, Boerwinkle E: Genetics of hypertension, target-organ complications, and response to therapy. Circulation 102(4), 40-45 (2000).
49. Rohrwasser A, Morgan T, Dillon HF et al.: Elements of a paracrine tubular renin-angiotensin system along the entire nephron. Hypertension 34, 1265-1274 (1999).
50. Navar LG, Harrison-Bernard LM, Nishiyama A, Kobori H: Regulation of intrarenal angiotensin II in hypertension. Hypertension 39 (Part 2), 316-322 (2002).
51. Bader M: Role of the local renin-angiotensin system in cardiac damage: a minireview focussing on transgenic animal models. J. Mol. Cell. Cardiol. 34, 1455-1462 (2002).
52. Varagic J, Frohlich ED: Local cardiac renin-angiotensin system: hypertension and cardiac failure. J. Mol. Cell. Cardiol. 34, 1435-1442 (2002).
53. Luft FC: Tissue renin-angiotensin system and end-organ damage. J. Mol. Med. 80(6), 325-326 (2002).
54. Neri Serneri GG, Boddi M, Coppo M et al.: Evidence for the existence of a functional cardiac renin-angiotensin system in humans. Circulation 94, 1886-1893 (1996).
55. Mizuiri S, Hemmi H, Kumanomidou H et al.: Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression. Kidney Int. 60, 1124-1130 (2001).
56. Mizuiri S, Yoshikawa H, Tanegashima M et al.: Renal ACE immunohistochemical localization in NIDDM patients with nephropathy. Am. J. Kidney Dis. 31(2), 301-307 (1998).
57. Cox R, Bouzehri N, Martin S et al.: Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides. Hum. Mol. Genet. 11(23), 2969-2977 (2002).
58. Leri A, Liu Y, Li B et al.: Up-regulation of AT(1) and AT(2) receptors in postinfarcted hypertrophied myocytes and strech-mediated apoptotic cell death. Am. J. Pathol. 156(5), 1663-1672 (2000).
59. Huang W, Gallois Y, Bouby N et al.: Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc. Natl. Acad. Sci. 98(23), 13330-13334 (2001).
60. Danser AHJ, Maarten ADH, Schalekamp MD et al.: Angiotensin-converting enzyme in the human heart. Circulation 92, 1387-1388 (1995).
61. Ferrandi M, Salardi S, Tripodi MG et al.: Evidence for an Interaction between adducin and Na, K-ATPase relation to genetic hypertension. Am. J. Physiol. 277(46), H1338-H1349 (1999).
62. Tripodi MG, Valtorta F, Torielli L et al.: Hypertension-associated point mutations in the adducin α and β subunits affect actin cytoskeleton and ion transport. J. Clin. Invest. 97(12), 2815-2822 (1996).
63. Butler R: The DD-ACE genotype and cardiovascular disease. Pharmacogenomics 1(2), 153-167 (2000).
64. van der Kleij FGH, Navis G, Kistemaker TJ, Apperloo AJ, de Zeeuw D, de Jong PE: Impact of the pre-intervention rate of renal function decline on benefit of renoprotective intervention. In: Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism and Renal Disease. Thesis Book. Rijksuniversiteit Groningen (Ed.) (2002).
65. Pontremoli R, Ravera M, Viazzi F et al.: Genetic polymorphism of the renin angiotensin system and organ damage in essential hypertension. Kidney Int. 57, 561-569 (2000).
66. Staessen JA, Wang JG, Ginocchio G et al.: The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J. Hypertens. 15 (12 pt 2), 1579-1592 (1997).
67. Morrison AC, Bray MS, Folsom AR, Boerwinkle E: ADD1 460W allele associated with cardiovascular disease in hypertensive individuals. Hypertension 39(6), 1053-1057 (2002).
68. Laragh JH, Letcher RL, Pickering TJ: Renin profiling for diagnosis and treatment of hypertension. JAMA 241, 151-156 (1979).
69. Laragh JH, Sealey JE: Renin system understanding for analysis and treatment of hypertensive patients: a means to quantify the vasoconstrictor elements, diagnose curable renal and adrenal causes, assess risk of cardiovascular morbidity, and find the best-fit drug regimen. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 2). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 1813-1836 (1995).
70. Blumenfeld JD, Laragh JH: Renin system analysis: a rationale method for the diagnosis and treatment of the individual patient with hypertension. Am. J. Hypertens. 11, 894-896 (1998).
71. Hollenberg NK: Set point for sodium homeostasis: surfeit, deficit, and their implications. Kidney Int. 17, 423-429 (1980).
72. Chobanian AV, Hill M: National Heart, Lung, and Blood Institute workshop on sodium and blood pressure. Hypertension 35, 858-863 (2000).
73. Cohen HW, Alderman MH: Low sodium diet after DASH: has the situation changed? Dietary approaches to stop hypertension. Curr. Hypertens. Rep. 4(4), 329-332 (2002).
74. Graudal NA, Galløe AM, Garred P: Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols and triglyceride. JAMA 279(17), 1383-1391 (1998).
75. Zanchetti A, Agabiti Rosei E, Dal Palù C, Leonetti G, Magnani B, Pessina A: The verapamil in hypertension and atherosclerosis study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J. Hypertens. 16(11), 1667-1676 (1998).
76. Lakshman MR, Reda DJ, Materson BJ, Cushman WC, Freis ED: Diuretics and beta-blockers do not have adverse effects at 1 year on plasma lipid and lipoprotein profiles in men with hypertension. Department of affairs cooperative study group on antihypertensive agents. Arch. Intern. Med. 159(6), 551-558 (1999).
77. Bianchi G, Tenconi IT, Lucca R: Effect in the conscious dog of constriction of the renal artery to a sole remaining kidney on haemodynamics, sodium balance, body fluid volumes, plasma renin concentration and pressor responsiveness to angiotensin. Clin. Sci. 38, 741-766 (1970).
78. Guyton AC, Hall JE, Coleman TG, Manning RD, Jr, Norman RA, Jr: The dominant role of the kidneys in long-term arterial pressure regulation in normal and antihypertensive states. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 1). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 1311-1326 (1995).
79. Guyton AC: Dominant role of the kidneys and accessory role of whole-body autoregulation in the pathogenesis of hypertension. Am. J. Hypertens. 2, 575-585 (1989).
80. Schmieder RE, Beil AH: Salt intake and cardiac hypertrophy. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 1). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 1327-1333 (1995).
81. Watkins BE, Davis JM, Freeman RH, De Forrest JM, Stephens GA: Continuous angiotensin II blockade throughout the acute phase of one-kidney hypertension in dog. Circ. Res. 42, 813-821 (1978).
82. Bing RF, Russell GI, Swales JD, Thurston H: Effects of 12-hour infusions of saralasin or captopril on blood pressure in hypertensive conscious rats. Relationship to plasma renin, duration of hypertension, and effect of unclipping. J. Lab. Clin. Med. 98, 302-310 (1981).
83. Freeman RH, Davis JO, Watkins BE, Stephens GA, De Forrest JM: Effects of continuous converting enzyme blockade on renovascular hypertension in the rat. Am. J. Physiol. 236(1), F21-F24 (1979).
84. Edmunds ME, Russel GI, Bing RF: Reversal of experimental renovascular hypertension. J. Hypertens. 9, 289-301 (1991).
85. Oelkers W, Diederich S: Primary hyperaldosteronism without suppressed renin due to secondary hypertensive kidney damage. J. Clin. Endocrinol. Metab. 85, 3266-3270 (2000).
86. Mulvany MJ: Structural changes in the resistance vessels in human hypertension. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 1). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 503-513 (1995).
87. Stowasser M: Hyperaldosteronism: primary versus tertiary. J. Hypertens. 20(1), 17-19 (2002).
88. Lund-Johansen P, Omvik P: Hemodynamic patterns of untreated hypertensive disease. In: Hypertension Pathophysiology, Diagnosis, and Management (Vol. 1). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 323-342 (1995).
89. Beretta-Piccoli C, Weidmann P, Brown JJ, Davies DL, Lever AF, Robertson JIS: Body sodium blood volume state in essential hypertension: abnormal relation of exchangeable sodium to age and blood pressure in male patients. J. Cardiovasc. Pharmacol. 6, S134-S142 (1984).
90. Meier A, Gubelin U, Weidmann P et al.: Age-rated profile of cardiovascular reactivity to norepinephrine and angiotensin II in normal and hypertensive man. Klin. Wochenschr. 58(21), 1183-1188 (1980).
91. Lund-Johansen P: Haemodynamics of essential hypertension. In: Textbook of Hypertension. Swales JD (Ed.), Blackwell Scientific Publications, Oxford, UK 61-76 (1994).
92. Julius S: The changing relationship between autonomic control and haemodynamics of hypertension. In: Textbook of Hypertension. Swales JD (Ed.), Blackwell Scientific Publications, Oxford, UK 77-84 (1994).
93. Walker BR, Padfield PL: Renin subgroups of hypertension. Textbook of Hypertension. Swales JD (Ed.), Blackwell Scientific Publications, Oxford, UK 735-740 (1994).
94. Bianchi G, Ferrari P: Renal factors involved in the pathogenesis of genetic forms of hypertension. Genetic Hypertens. 218, 447-458 (1992).
95. Luft FC, Weinberger MH, Fineberg NS, Miller JZ, Grim CE: Effects of age on renal sodium homeostasis and its relevance to sodium sensitivity. Am. J. Med. 82 (1B), 9-15 (1987).
96. Ferri C, Bellini C, Desideri G et al.: Relationship between insulin resistance and nonmodulating hypertension, linkage of metabolic abnormalities and cardiovascular risk. Diabetes 48, 1623-1630 (1999).
97. Jamerson KA: rationale for angiotensin II receptor blockers in patients with low-renin hypertension. Am. J. Kidney Dis. 36 (3 Suppl. 1), S24-S30 (2000).
98. Aviv A: Salt consumption, reactive oxygen species and cardiovascular ageing: a hypothetical link. J. Hypertens. 20(4), 555-559 (2002).
99. Glazier AM, Nadeau JH, Aitman TJ: Finding genes that underlie complex traits. Science 298, 2345-2349 (2002).
100. Willett WC: Balancing life-style and genomics research for disease prevention Science 296, 695-698 (2002).
101. Schork NJ: Genetically complex cardiovascular traits: origins, problems, and potential solutions. Hypertension 29 (pt 2), 145-149 (1997).
102. Duboule D, Wilkins AS: The evolution of 'bricolage'. Trends Genet. 14, 54-59 (1998).
103. Cusi D, Barlassina C, Azzani T et al.: α-adducin polymorphism in primary hypertension: linkage and association study: relationship to salt sensitivity. Lancet 349, 1353-1357 (1997).
104. Glorioso N, Manunta P, Filigheddu F et al.: The role of α-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study. Hypertension 34, 649-654 (1999).
105. Glorioso N, Filigheddu F, Cusi D et al.: α-adducin 460Trp allele is associated with erythrocyte Na transport rate in primary hypertension. Hypertension 39 (Part 2), 357-362 (2002).
106. Sharma AM: The thrifty-genotype hypothesis and its implications for the study of complex genetic disorders in man. J. Mol. Med. 76(8), 568-571 (1998).
107. Bianchi G, Baldoli E, Lucca E, Barbin P: Pathogenesis of arterial hypertension after the constriction of the renal artery leaving the opposite kidney intact both in the anaesthetized and the conscious dog. Clin. Sci. 42, 651-664 (1972).
108. Ferrari P, Cusi D, Barber B et al.: Erythrocyte membrane and renal function in relation to hypertension in rats of the Milan hypertensive strain. Clin. Sci. 63, 61S-64S (1982).
109. Kyriakis JM: Life-or-death decisions. Nature 414, 265-266 (2001).
110. Ingolia NT Murray AW. History Matters. Science 297, 948-949 (2002).
111. Sciarrone MT, Stella P, Barlassina C et al.: ACE and α-adducin polymorphism as markers of individual response to diuretic therapy. Hypertension 41, 398-403 (2003).
112. Staessen JA, Wang JG, Brand E et al.: Effects of free candidate genes on prevalence and incidence of hypertension in a Caucasian population. J. Hypertens. 19, 1349-1358 (2001).
113. Wang J, Staessen JA, Tizzoni L et al.: Renal function in relation to three candidate genes. Am. J. Kidney. Dis. 38(6), 1158-1168 (2001).
114. Balkestein EJ, Wang JG, Struijker-Boudier HA et al.: Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population. J. Hypertens. 20(8), 1551-1561 (2002).
115. Frankel WN, Schork NJ: Who's afraid of epistasis? Nat. Genet. 14, 371-373 (1996).
116. Cordell HJ: Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans. Hum. Mol. Genet. 11(20), 2463-2468 (2002).
117. Kajiwara K, Berson EL, Dryja TP: Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science 264 (5165), 1604-1608 (1994).
118. Tienari PJ, Terwilliger JD, Ott J, Palo J, Peltonen L: Two-locus linkage analysis in multiple sclerosis (MS). Genomics 19(2), 320-325 (1994).
119. Fessele S, Maier H, Zischek C, Nelson PJ, Werner T: Regulatory context is a crucial part of gene function. Trends in Genet. 18, 60-63 (2002).
120. Weiss K: Goings on in Mendel's garden. Evol. Anthropol. 11, 40-44 (2002).
121. Samani NJ, Thompson JR, O'Toole L, Channer K, Woods KL: A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation 94(4), 708-712 (1996).
122. Wang JG, Staessen JA: Genetic polymorphisms in the renin-angiotensin system: relevance for susceptibility to cardiovascular disease. Eur. J. Pharmacol. 410 (2-3), 289-302 (2000).
123. van der Kleij FG, de Jong PE, Henning RH, de Zeeuw D, Navis G: Enhanced responses of blood pressure, renal function, and aldosterone to angiotensin I in the DD genotype are blunted by low sodium intake. J. Am. Soc. Nephrol. 13(4), 1025-1033 (2002).
124. Frindt G, Masilamani S, Knepper MA, Palmer LG: Activation of epithelial Na channels during short-term Na deprivation. Am J Physiol Renal Physiol 280, F112-F118 (201).
125. Masilamani S, Wang X, Kim GH et al.: Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC abundance changes with dietary NaCl restriction. Am. J. Physiol. Renal. Physiol. 283, F648-F657 (2002).
126. Rossier BC, Pradervand S, Schild L, Hummler E: Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors. Ann. Rev. Physiol. 64, 877-897 (2002).
127. Liljedahl U, Karlsson J, Melhus H et al.: A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response. Pharmacogenetics 13, 7-17 (2003).
128. Terwilliger JD, Haghighi F, Hiekkalinna TS, Göring HHH: A biased assessment of the use of SNPs in human complex traits. Curr. Opin. Genet. Dev. 12, 726-734 (2002).
129. Barlassina C, Schork NJ, Manunta P et al.: Synergistic effect of α-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion. Kidney Int. 57(3), 1083-1090 (2000).
130. Psaty BM, Smith NL, Heechberty SR et al.: Diuretic therapy, the α-adducin gene variant and the risk of myocardial infarction or stroke in persons with treated hypertension. JAMA 287(13), 1680-1689 (2002).
131. Lachurié ML, Azizi M, Guyene TT, Alhenc-Gelas F, Menard J: Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. Circulation 91, 2933-2942 (1995).
132. Steeds RP, Wardle A, Smith PD, Martin D, Channer KS, Samani NJ: Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction. Atherosclerosis 154(1), 123-128 (2001).
133. Peterlin B, Milanez T, Kobal J et al.: DD genotype of the angiotensin-converting enzyme gene and stroke in Slovenian population. Pflugers Arch. 439 (Suppl. 3), R38-R39 (2000).
134. Lin JJ, Yueh KC, Lin GY et al.: Lack of association between angiotensin I-converting enzyme gene deletion polymorphism and cerebrovascular disease in Taiwanese. J. Formos. Med. Assoc. 99(12), 895-901 (2000).
135. Concato J, Shah N, Horwitz RI: Randomized controlled trials, observational studies and the hierarchy of research designs. N. Engl. J. Med. 342(25), 1887-1892 (2000).
136. Poynard T, Munteanu M, Ratziu V, Martino V, Taieb J, Opolon P: Truth survival in clinical research: an evidence-based requiem? Ann. Intern. Med. 136, 888-8895 (2002).
137. Holtzman NA, Marteau TM: Will genetics revolutionize medicine? N. Engl. J. Med. 343(2), 141-144 (2000).
138. Ferrari P, Bianchi G: Genetic mapping and tailored antihypertensive therapy. Cardiovasc. Drugs Ther. 14, 387-395 (2000).
139. He FJ, Markandu ND, Mac Gregor GA: Importance of the renin system for determining blood pressure fall with acute salt restriction in hypertensive and normotensive whites. Hypertension 38, 321-325 (2001).
140. Beermann B, Groschinsky-Grind M: Antihypertensive effect of various doses of hydrochlorothiazide and its relation to the plasma level of the drug. Eur. J. Clin. Pharmacol. 13, 195-201 (1978).
141. Wang JG, Staessen JA, Barlassina C et al.: Association between hypertension and variation in the α and β-adducin genes in a white population. Kidney Int. 62(6), 2152-2159 (2002).
142. Hall JB, Brands MW. Intrarenal and circulating angiotensin II and renal function. In: The Renin-Angiotensin System. Robertson J, Nicholls MG (Ed.), Gower Medical Publishing, New York, USA 26.1-26.43 (1993).
143. Harris PJ, Hiranyachattada S, Antoine AM, Walker L, Reilly AM, Eitle E: Regulation of renal tubular sodium transport by angiotensin II and atrial natriuretic factor. Clin. Exp. Pharmacol. Physiol. 3, S112-S118 (1996).
144. 1 Receptors. J. Am. Soc. Nephrol. 13, 1131-1135 (2002).
145. Sechi LA, Griffin CA, Giachetti G et al.: Tissue-specific regulation of Type 1 angiotensin II receptor mRNA levels in the rat. Hypertension 28(3), 403-408 (1996).
146. Poch E, Gonzáles D, Giner V, Bragulat E, Coca A, de la Sierra A: Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. Hypertension 38, 1204-1209 (2001).
147. Giner V, Poch E, Bragulat E et al.: Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension. Hypertension 35(Part 2), 512-517 (2000).
148. Dengel DR, Brown MD, Ferrel RE, Supiano MA: Role of angiotensin converting enzyme genotype in sodium sensitivity in older hypertensives. Am. J. Hypertens. 14, 1178-1184 (2001).
149. Turner ST, Boerwinkle E, Sing CF: Context-dependent associations of the ACE I/D polymorphism with blood pressure. Hypertension 34(Part 2), 773-778 (1999).
150. Jeunemaitre X, Soubrier F, Kotelevtsev YV et al.: Molecular basis of human hypertension: role of angiotensinogen. Cell 71(1), 169-180 (1992).
151. Fernadez-Arcas N, Dieguez-Lucena JL, Munoz-Moran E et al.: Both alleles of the M235T polymorphism of the angiotensinogen gene can be a risk factor for myocardial infarction. Clin. Genet. 60(1), 52-57 (2001).
152. Staessen JA, Kuznetsova T, Wang JG, Emelianov D, Vlietinck R, Fagard R: M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J. Hypertens. 17(1), 9-17 (1999).
153. Hunt SC, Geleijnse JM, Wu LL, Witteman JCM, Williams RR, Grobbee DE: Enhanced blood pressure response to mild sodium reduction in subjects with the 235T variant of the angiotensinogen gene. Am. J. Hypertens. 12, 460-466 (1999).
154. Svetkey LP, Moore TJ, Simons-Morton DG et al.: Angiotensinogen genotype and blood pressure response in the dietary approaches to stop hypertension (DASH) study. J. Hypertens. 19, 1949-1956 (2001).
155. Johnson AG, Nguyen TV, Davis D: Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in mormotensive and hypertensive elderly subjects. J. Hypertens. 19, 1053-1060 (2001).
156. O'Toole L, Steward M, Padfield P, Canner K: Effect of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene on response to angiotensin-converting enzyme inhibitors in patients with heart failure. J. Cardiovasc. Pharmacol. 32, 988-994 (1998).
157. Nakano Y, Oshima T, Watanabe M, Matsuura H, Kajiyama G, Kambe M: Angiotensin I-converting enzyme gene polymorphism and acute response to captopril in essential Hypertension. Am. J. Hypertens. 10(9 pt 1), 1064-1068 (1997).
158. Ueda S, Meredith PA, Morton JJ, Connell JM, Elliott HL: ACE (I/D) genotype as a predictor of the magnitude and duration of the response to an ACE inhibitor drug (enalaprilat) in humans. Circulation 98(20), 2148-2153 (1998).
159. Ohmichi N, Iwai N, Uchida Y, Shichiri G, Nakamura Y, Kinoshita M: Relationship between the response to the angiotensin converting enzyme inhibitor imidapril and the angiotensin converting enzyme genotype. Am. J. Hypertens. 10(8), 951-955 (1997).
160. Siffert W, Rosskopf D, Siffert G et al.: Association of a human G-protein β3 subunit variant with hypertension. Nat. Genet. 18, 45-48 (1998).
161. Siffert W, Düsing R: Sodium-proton exchange and primary hypertension. An update. Hypertension 26(4), 649-655 (1995).
162. Schunkert H, Hense HW, Döring A, Riegger GAJ, Siffert W: Association between a polymorphism in the G protein β3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension 32, 510-513 (1998).
163. Brand E, Herrmann SM, Nicaud V et al.: The 825C/T polymorphism of the G-protein subunit β3 is not related to hypertension. Hypertension 33, 1175-1178 (1999).
164. Turner ST Schwartz GL, Chapman AB, Boerwinkle E: C825T Polymorphism of the G protein β3-subunit and antihypertensive response to a thiazide diuretic. Hypertension 37 (part 2), 739-743 (2001 ).
165. Schorr U, Blaschke K, Beige J, Distler A, Sharma AM: G-protein β3 subunit 825T allele and response to dietary salt in normotensive men. J. Hypertens. 18, 855-859 (2000).
166. Reich DE, Schaffner SF, Daly MJ et al.: Human genome sequence variation and the influence of gene history, mutation and recombination. Nat. Genet. 32, 135-142 (2002).
167. Jorde LB, Vatkins WS, Bamshad MJ: Population genomics: a bridge from evolutionary history to genetic medicine. Hum. Mol. Gen. 10(20), 2199-2207 (2001).
168. Perls T, Kunkel LM, Puca AA: The genetics of exceptional human longevity. J. Am. Geriatr. Soc. 50, 359-368 (2002).
169. Ferrari P, Bianchi G: Lessons from experimental genetic hypertension. In: Hypertension: Pathophysiology, Diagnosis and Management (Vol. 1). Laragh JH, Brenner BM (Eds), Raven Press Publishers, New York, USA 1261-1279 (1995).
170. Bianchi G, Tripodi MG, Casari G et al.: Two point mutations within the adducin genes are involved in blood pressure variation. Proc. Natl. Acad. Sci. 91, 3999-4003 (1994).
171. Casari G, Barlassina C, Cusi D et al.: Association of the α-adducin locus with essential hypertension. Hypertension 25(3), 320-326 (1995).
172. Ferrandi M, Minotti E, Salardi S, Florio M, Bianchi G, Ferrari P: Ouabain like factor in the Milan hypertensive rats (MHS). Am. J. Physiol. 263, 739-748 (1992).
173. Manunta P, Stella P, Rivera R et al.: Left ventricle mass, stroke volume and ouabain-like factor in essential hypertension. Hypertension 34, 450-456 (1999).
174. Pierdomenico SD, Bucci A, Manunta P et al.: Endogenous ouabain and haemodynamic and left ventricular geometric patterns in essential hypertension. Am. J. Hypertens. 14, 44-50 (2001).
175. Ferrandi M, Manunta P, Balzan S, Hamlyn JM, Bianchi G, Ferrari P: Ouabain-like factor quantification in mammalian tissues and plasma. Comparison of two independent assays. Hypertension 30(4), 886-896 (1997).
176. Hamlyn JM, Lu ZR, Manunta P et al.: Observations on the nature, biosynthesis, secretion and significance of endogenous ouabain. Clin. Exp. Hypertens. 20 (5-6), 523-533 (1998).
177. +) ATPase associated with essential hypertension. Nature 300(5893), 650-652 (1982),
178. Schoner W. Endogenous cardiac glycosides, a new class of steroid hormones. Eur. J. Biochem. 269(10), 2440-2448 (2002).
179. Gottlieb SS, Rogowski AC, Weinberg M, Krichten CM, Hamilton BP, Hamlyn JM: Elevated concentrations of endogenous ouabain in patients with congestive heart failure. Circulation 86(2), 420-425 (1992).
180. Manunta P, Cusi D, Barlassina C et al.: α-adducin polymorphisms and renal sodium handling in essential hypertensive patients. Kidney Int. 53, 1471-1478 (1998).
181. Manunta P, Burnier M, D'Amico M et al.: Adducin polymorphism affects renal proximal tubule reabsorption in hypertension. Hypertension 33, 694-697 (1999).
182. Manunta P, Messaggio E, Ballabeni C et al.: Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension. Hypertension 38, 198-203 (2001).
183. Schork NJ, Chakravati A, Thiel B et al.: Lack of association between a biallelic polymorphism in the adducin gene and blood pressure in whites and African Americans. Am. J. Hypertens. 13, 693-698 (2000).
184. Busjajn A, Aydin A, von Treuenfels N et al.: Linkage but lack of association for blood pressure and the α-adducin locus in normotensive twins. J. Hypertens. 17, 1437-1441 (1999).
185. Busch CP, Ramdath DD, Ramsewak S, Hegele RA: The ADDI G460W polymorphism is not associated with variation in blood pressure in Canadian Oji-Cree. J. Hum. Genet. 44, 225-229 (1999).
186. Bianchi G, Baer PG, Fox U, Duzzi L, Pagetti D, Giovannetti AM: Changes in renin, water balance, and sodium balance during development of high blood pressure in genetically hypertensive rats. Circulation Res. 36 & 37(Suppl. 1), 153-161 (1975).
187. Salvati P, Pinciroli GP, Bianchi G: Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain at different ages. J Hypertens. 2(Suppl. 3), 351-353 (1984).
188. Boberg U, Persson AEG: Increased tubuloglomerular feedback activity in Milan hypertensive rats. Am J Physiol 250, F967-F974 (1986).
189. Ferrandi M, Tripodi MG., Salardi S et al.: Renal Na, K-ATPase in genetic hypertension. Hypertension 28(6), 1018-1025 (1996).
190. Melzi ML, Bertorello A, Fukuda Y, Muldin I, Sereni F, Aperia A: Na, K-ATPase activity in renal tubule cells from Milan hypertensive rats. Am. J. Hypertens. 2(7), 563-566 (1989).
191. Kumar S, Hedges SB: A molecular timescale for vertebrate evolution. Nature 392, 917-920 (1998).
192. Ferrari P, Torielli L, Ferrandi M. et al.: PST 2238: A new antihypertensive compound that antagonizes the long-term pressor effect of ouabain. J. Pharmacol. Exp. Ther. 285(1), 83-94 (1998).
193. Quadri L, Bianchi G, Cerri A et al.: 17β-(3- Furyl)-5β-androstane-3β, 14β, 17α-triol (PST 2238). A very potent antihypertensive agent with a novel mechanism of action. J. Med. Chem. 40(11), 1561-1564 (1997).
194. Ferrari P, Ferrandi M, Tripodi MG et al.: PST 2238. A new antihypertensive compound that modulates Na, K-ATPase in genetic hypertension. J. Pharm. Exp. Ther. 288(3) 1074-1083 (1999).
195. Ferrandi M, Barassi P, Minotti E et al.: PST 2238: a new antihypertesive compound that modulates renal NA-K pump function without diuretic activity in Milan hypertensive rats. J. Cardiovasc. Pharmacol, 40, 881-889 (2002).