(Hypertension. 2000;35:694.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
CYP11B2 Gene Polymorphisms in Idiopathic Hyperaldosteronism
From the Department of Medicine and Experimental Oncology (P.M., D.S., F.R., L.C., F.V.), Hypertension Unit, University of Torino, Torino, Italy; Department of Medical and Surgical Sciences (F.F., C.P.), Division of Endocrinology, University of Padova, Padova, Italy; and Fondation Jean Dausset CEPH (L.P.), Paris, France.
Correspondence to Dr Paolo Mulatero, University of Torino, Department of Medicine and Experimental Oncology, Hypertension Unit, San Vito Hospital, S San Vito 34, 10133 Torino, Italy. E-mail mulatero{at}tin.it
Abstract—Primary aldosteronism is characterized by autonomous production of aldosterone and arterial hypertension, and it occurs in 2 principal forms: aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). APA can be cured through removal of the adenoma, whereas IHA leads to hypertension that must be treated with medication. The origin of the autonomous aldosterone production in IHA is poorly understood, but genetic factors may contribute to its cause. To test the hypothesis that variants of the aldosterone synthase gene may contribute to susceptibility to IHA, we compared genotypes at 3 polymorphic sites in the CYP11B2 gene in patients with IHA (n=90) with those found in patients with APA (n=38), in patients with essential hypertension (n=72), and in normotensive individuals (n=102). We observed significant linkage disequilibrium among the 3 polymorphisms with 2 frequent haplotypes in all groups studied. One haplotype (C2R) was found to be increased in frequency in the IHA group (47%) compared with the other groups, which had a similar haplotype frequency (36%). The 3 polymorphisms studied have been implicated in either essential hypertension or excess aldosterone production in previous studies. Because of the strong linkage disequilibrium, the observed results could be due to the action of any 1 of the 3 alleles or to another allele in linkage disequilibrium with them. Our results suggest that variations in the CYP11B2 gene may contribute to dysregulation of aldosterone synthesis and lead to susceptibility to IHA.
Key Words: aldosterone • hypertension, essential • hyperaldosteronism • genetics • polymorphism
This article has been cited by other articles:
 |
|
 |
|
  E. Ritz How Little Aldosterone is Able to Raise Blood Pressure? Clin. J. Am. Soc. Nephrol., April 1, 2009; 4(4): 703 - 710. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Makhanova, J. Hagaman, H.-S. Kim, and O. Smithies Salt-Sensitive Blood Pressure in Mice With Increased Expression of Aldosterone Synthase Hypertension, January 1, 2008; 51(1): 134 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mulatero, F. Veglio, P. Maffei, M. Bondanelli, S. Bovio, F. Daffara, G. Leotta, A. Angeli, C. Calvo, C. Martini, et al. CYP11B2 -344T/C Gene Polymorphism and Blood Pressure in Patients with Acromegaly J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5008 - 5012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tanahashi, T. Mune, Y. Takahashi, M. Isaji, T. Suwa, H. Morita, N. Yamakita, K. Yasuda, T. Deguchi, P. C. White, et al. Association of Lys173Arg Polymorphism with CYP11B2 Expression in Normal Adrenal Glands and Aldosterone-Producing Adenomas J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6226 - 6231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Grim, A. W. Cowley Jr, P. Hamet, D. Gaudet, M. L. Kaldunski, J. M. Kotchen, S. Krishnaswami, Z. Pausova, R. Roman, J. Tremblay, et al. Hyperaldosteronism and Hypertension: Ethnic Differences Hypertension, April 1, 2005; 45(4): 766 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. White and W. E. Rainey Polymorphisms in CYP11B Genes and 11-Hydroxylase Activity J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1252 - 1255. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Williams, P. Mulatero, M. Bosio, S. Lewicka, M. Palermo, F. Veglio, and D. Armanini A Particular Phenotype in a Girl with Aldosterone Synthase Deficiency J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3168 - 3172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M.C. Connell, R. Fraser, S. MacKenzie, and E. Davies Is Altered Adrenal Steroid Biosynthesis a Key Intermediate Phenotype in Hypertension? Hypertension, May 1, 2003; 41(5): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Lim, T. M. Macdonald, C. Holloway, E. Friel, N. H. Anderson, E. Dow, R. T. Jung, E. Davies, R. Fraser, and J. M. C. Connell Variation at the Aldosterone Synthase (CYP11B2) Locus Contributes to Hypertension in Subjects with a Raised Aldosterone-to-Renin Ratio J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4398 - 4402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Mulatero, T. A. Williams, A. Milan, C. Paglieri, F. Rabbia, F. Fallo, and F. Veglio Blood Pressure in Patients with Primary Aldosteronism Is Influenced by Bradykinin B2 Receptor and {alpha}-Adducin Gene Polymorphisms J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3337 - 3343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-J. Shi, H. T. Nguyen, G. D. Sharma, L. G. Navar, and K. N. Pandey Genetic disruption of atrial natriuretic peptide receptor-A alters renin and angiotensin II levels Am J Physiol Renal Physiol, October 1, 2001; 281(4): F665 - F673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. El-Gharbawy, V. S. Nadig, J. M. Kotchen, C. E. Grim, K. B. Sagar, M. Kaldunski, P. Hamet, Z. Pausova, D. Gaudet, F. Gossard, et al. Arterial Pressure, Left Ventricular Mass, and Aldosterone in Essential Hypertension Hypertension, March 1, 2001; 37(3): 845 - 850. [Abstract] [Full Text] [PDF]
|
|