Skip to main content

Advertisement

SpringerLink
Log in

Genetic information in the diagnosis and treatment of hypertension

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Advancement in cardiovascular science should be measured by a number of new diagnostic and therapeutic options applied in clinical practice as a result of translational research. Hypertension genetics is a good example of such a successful transfer of knowledge from bench to bedside. There are genetic methods currently used as diagnostic tools in patients presenting with secondary forms of hypertension, including primary hyperaldosteronism, Cushing’s syndrome, pheochromocytoma, and chronic kidney disease. Directed treatment that corrects pathophysiologic abnormalities is available for several monogenic forms of hypertension as a result of uncovering their underlying genetic mechanisms. Progress in hypertension pharmacogenetics and pharmacogenomics brings closer a perspective of personalized antihypertensive treatment and gene transfer strategies, which, although still considered as innovative approaches, may soon become options to treat, control, and, possibly, cure hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Omura M, Saito J, Yamaguchi K, et al.: Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens Res 2004, 27:193–202.

    Article  PubMed  Google Scholar 

  2. Lifton RP, Dluhy RG, Powers M, et al.: A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992, 355:262–265.

    Article  PubMed  CAS  Google Scholar 

  3. Mulatero P, Morello F, Veglio F: Genetics of primary aldosteronism. J Hypertens 2004, 22:663–670.

    Article  PubMed  CAS  Google Scholar 

  4. Dluhy RG, Anderson B, Harlin B, et al.: Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 2001, 138:715–720.

    Article  PubMed  CAS  Google Scholar 

  5. Lifton R, Gharavi A, Geller D: Molecular mechanisms of human hypertension. Cell 2001, 104:545–556.

    Article  PubMed  CAS  Google Scholar 

  6. New MI, Geller DS, Fallo F, et al.: Monogenic low renin hypertension. Trends Endocrinol Metab 2005, 16:92–97. A topical, concise review on clinical aspects of monogenic hypertension.

    Article  PubMed  CAS  Google Scholar 

  7. Stowasser M, Gordon R: Familial hyperaldosteronism. J Steroid Biochem Mol Biol 2001, 78:215–229.

    Article  PubMed  CAS  Google Scholar 

  8. MacConnachie AA, Kelly KF, McNamara A, et al.: Rapid diagnosis and identification of cross-over sites in patients with glucocorticoid remediable aldosteronism. J Clin Endocrinol Metab 1998, 83:4328–4331.

    Article  PubMed  CAS  Google Scholar 

  9. Adler G, Widecka K, Peczkowska M, et al.: Genetic screening for glucocorticoid-remediable aldosteronism (GRA): experience of three clinical centres in Poland. J Appl Genet 2005, 46:329–332.

    PubMed  Google Scholar 

  10. Groussin L, Horvath A, Jullian E, et al.: A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab 2006, 91:1943–1949. An excellent example of progress in cardiovascular genetics in uncovering mechanisms of endocrine diseases.

    Article  PubMed  CAS  Google Scholar 

  11. Libe R, Bertherat J: Molecular genetics of adrenocortical tumours, from familial to sporadic diseases. Eur J Endocrinol 2005, 153:477–487.

    Article  PubMed  CAS  Google Scholar 

  12. Groussin L, Jullian E, Perlemoine K, et al.: Mutations of the PRKAR1A gene in Cushing’s syndrome due to sporadic primary pigmented nodular adrenocortical disease. J Clin Endocrinol Metab 2002, 87:4324–4329.

    Article  PubMed  CAS  Google Scholar 

  13. Mulligan LM, Kwok JB, Healey CS, et al.: Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993, 363:458–460.

    Article  PubMed  CAS  Google Scholar 

  14. Mulligan LM, Eng C, Healey CS, et al.: Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN2A and FMTC. Nat Genet 1994, 6:70–74.

    Article  PubMed  CAS  Google Scholar 

  15. Wiesner GL, Snow-Bailey K: Multiple endocrine neoplasia type 2. http://140.142.26.27/servlet/access?db=geneclinic s&site=gt&id=8888891&key=fkWDBgv-gytUT&gry=& fcn=y&fw=p6V2&.lename=/profiles/men2/index.html. Accessed June 15, 2006. The most up-to-date information on genetic testing in patients with MEN2.

  16. Takahashi M, Asai N, Iwashita T, et al.: Molecular mechanisms of development of multiple endocrine neoplasia 2 by RET mutations. J Intern Med 1998, 243:509–513.

    PubMed  CAS  Google Scholar 

  17. Latif F, Tory K, Gnarra J, et al.: Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260:1317–1320.

    Article  PubMed  CAS  Google Scholar 

  18. Schimke RN, Collins DL, Stolle CA: Von Hippel-Lindau syndrome. http://140.142.26.27/servlet/access?db=genec linics&site=gt&id=8888892&key=rcP7MCsyeptb1&gry =&fcn=y&fw=HfTO&.lename=/profiles/vhl/index.html. Accessed June 15, 2006. The most up-to-date information on genetic testing in patients with von Hippel-Lindau syndrome.

  19. Stolle C, Glenn G, Zbar B, et al.: Improved detection of germline mutations in the von Hippel-Lindau disease tumour suppressor gene. Hum Mutat 1998, 12:417–423.

    Article  PubMed  CAS  Google Scholar 

  20. American Society of Clinical Oncology: American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 2003, 21:2397–2406.

    Article  Google Scholar 

  21. Ars S, Serra E, Garcia J, et al.: Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1. Hum Mol Genet 2000, 9:237–247.

    Article  PubMed  CAS  Google Scholar 

  22. Lama G, Graziano L, Calabrese E, et al.: Blood pressure and cardiovascular involvement in children with neurofibromatosis type 1. Pediatr Nephrol 2004, 19:413–418.

    Article  PubMed  Google Scholar 

  23. Lenders JWM, Eisenhofer G, Mannelli M, et al.: Pheochromocytoma. Lancet 2005, 366:665–675. A state-of-the-art review presenting current views on pathogenesis, diagnosis, and treatment of pheochromocytoma.

    Article  PubMed  Google Scholar 

  24. Friedman JM. Neurofibromatosis 1. http://140.142.26.27/ servlet/access?db=geneclinics&site=gt&id=8888892&key =3t6-IckLoIkR3&gry=&fcn=y&fw=lXJ7&filename=/profiles/nf1/index.html. Accessed June 15, 2006.

  25. Baysal BE, Willett-Brozick JE, Lawrence EC, et al.: Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet 2002, 39:178–183.

    Article  PubMed  CAS  Google Scholar 

  26. Neumann HP, Pawlu C, Peczkowska M, et al.: Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 2004, 292:943–951.

    Article  PubMed  CAS  Google Scholar 

  27. Baysal BE: Genomic imprinting and environment in hereditary paraganglioma. Am J Med Genet C Semin Med Genet 2004, 129:85–90.

    Article  PubMed  Google Scholar 

  28. Neumann HP, Bausch B, McWhinney SR, et al.: Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002, 346:1459–1466.

    Article  PubMed  CAS  Google Scholar 

  29. Amar L, Bertherat J, Baudin E, et al.: Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 2005, 23:8812–8818.

    Article  PubMed  CAS  Google Scholar 

  30. Steinman TI: Polycystic kidney disease: a new perspective from the beginning. Kidney Int 2005, 68:2398–2399.

    Article  PubMed  Google Scholar 

  31. Ong AC, Harris PC: Molecular pathogenesis of ADPKD: the polycystin complex gets complex. Kidney Int 2005, 67:1234–1247. An excellent summary of current knowledge about genetic and molecular mechanisms of ADPKD.

    Article  PubMed  CAS  Google Scholar 

  32. Kelleher CL, McFann KK, Johnson AM, et al.: Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens 2004, 17:1029–1034.

    Article  PubMed  Google Scholar 

  33. Chapman AM, Johnson S, Rainguet S, et al.: Left ventricular hypertrophy in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1997, 8:1292–1297.

    PubMed  CAS  Google Scholar 

  34. Nicolau C, Torra R, Badenas C, et al.: Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form. Nephrol Dial Transplant 2000, 15:1373–1378.

    Article  PubMed  CAS  Google Scholar 

  35. Sessa A, Ghiggeri GM, Turco AE: Autosomal dominant polycystic kidney disease: clinical and genetic aspects. J Nephrol 1997, 10:295–310.

    PubMed  CAS  Google Scholar 

  36. Perrone RD, Miskulin DC:. Hypertension in individuals at risk for autosomal dominant polycystic kidney disease: to screen or not to screen. Am J Kidney Dis 2005, 46:557–559. An excellent editorial containing critical evaluation of indications for genetic screening in ADPKD.

    Article  PubMed  Google Scholar 

  37. Stowasser M, Gordon RD: Primary aldosteronism: from genesis to genetics. Trends Endocrinol Metab 2003, 14:310–317.

    Article  PubMed  CAS  Google Scholar 

  38. Nabel EG:. Cardiovascular disease. N Engl J Med 2003, 349:60–72. A very up-to-date review on molecular mechanisms underlying cardiovascular diseases.

    Article  PubMed  CAS  Google Scholar 

  39. Jeunemaitre X, Bassilana F, Persu A, et al.: Genotype-phenotype analysis of a newly discovered family with Liddle’s syndrome. J Hypertens 1997, 15:1091–1100.

    Article  PubMed  CAS  Google Scholar 

  40. Furuhashi M, Kitamura K, Adachi M, et al.: Liddle’s syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit. J Clin Endocrinol Metab 2005, 90:340–344.

    Article  PubMed  CAS  Google Scholar 

  41. Baker EH, Duggal A, Dong Y, et al.: Amiloride, a specific drug for hypertension in black people with T594M variant? Hypertension 2002, 40:13–17.

    Article  PubMed  CAS  Google Scholar 

  42. Hollier JM, Martin DF, Bell DM, et al.: Epithelial sodium channel allele T594M is not associated with blood pressure or blood pressure response to amiloride. Hypertension 2006, 47:428–433.

    Article  PubMed  CAS  Google Scholar 

  43. Wilson FH, Disse-Nicodeme S, Choate KA, et al.: Human hypertension caused by mutations in WNK kinases. Science 2001, 293:1107–1112.

    Article  PubMed  CAS  Google Scholar 

  44. Zhang H, Staessen JA: Association of blood pressure with genetic variation in WNK kinases in a white European population. Circulation 2005, 112:3371–3372.

    Article  PubMed  Google Scholar 

  45. Mayan H, Vered I, Mouallem M, et al.: Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J Clin Endocrinol Metab 2002, 87:3248–3254.

    Article  PubMed  CAS  Google Scholar 

  46. Tobin MD, Raleigh SM, Newhouse S, et al.: Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population. Circulation 2005, 112:3423–3429.

    Article  PubMed  CAS  Google Scholar 

  47. Turner ST, Schwartz GL, Chapman AB, et al.: WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension 2005, 46:758–765.

    Article  PubMed  CAS  Google Scholar 

  48. Kurland L, Lind L, Melhus H: Using genotyping to predict responses to anti-hypertensive treatment. Trends Pharmacol Sci 2005, 26:443–447. An interesting review that highlights current concepts and challenges of current hypertension pharmacogenetics.

    PubMed  CAS  Google Scholar 

  49. Cadman PE, O’Connor DT: Pharmacogenomics of hypertension. Curr Opin Nephrol Hypertens 2003, 12:61–70.

    Article  PubMed  CAS  Google Scholar 

  50. Siest G, Marteau JB, Maumus S, et al.: Pharmacogenomics and cardiovascular drugs: need for integrated biological system with phenotypes and proteomic markers. Eur J Pharmacol 2005, 527:1–22.

    Article  PubMed  CAS  Google Scholar 

  51. Maitland-van der Zee AH, Turner ST, Schwartz GL, et al.: A multilocus approach to the antihypertensive pharmacogenetics of hydrochlorothiazide. Pharmacogenet Genomics 2005, 15:287–93.

    Article  PubMed  CAS  Google Scholar 

  52. Maitland-van der Zee AH, Turner ST, Schwartz GL, et al.: Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects. Am J Hypertens 2005, 18:1077–1083.

    Article  PubMed  CAS  Google Scholar 

  53. Padmanabhan S, Wallace C, Munroe PB, et al.: Chromosome 2p shows significant linkage to antihypertensive response in the British Genetics of Hypertension Study. Hypertension 2006, 47:603–608. One of the first examples of a successful pharmacogenomic approach in studies on hypertension.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126, University Place, G12 8TA, Glasgow, UK

    Anna F. Dominiczak MD

Authors
  1. Maciej Tomaszewski MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lukas Zimmerli MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fadi J. Charchar PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna F. Dominiczak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna F. Dominiczak MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tomaszewski, M., Zimmerli, L., Charchar, F.J. et al. Genetic information in the diagnosis and treatment of hypertension. Current Science Inc 8, 309–316 (2006). https://doi.org/10.1007/s11906-006-0070-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-006-0070-3

Keywords

Search

Navigation