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Relationship of aldosterone synthase gene (C-344T) and mineralocorticoid receptor (S810L) polymorphisms with gestational hypertension

Journal of Human Hypertension volume 25, pages 320–326 (2011)Cite this article

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Abstract

The extent of genetic influence in the aetiology of gestational hypertension has not been completely determined. The aim of this study was to analyse the relationship between aldosterone levels and the -344T/C polymorphism of the aldosterone synthase gene (CYP11B2) and to investigate the frequency of the S810L mutation of mineralocorticoid receptor (MR) in gestational hypertension. One hundred women with pregnancy-induced hypertension and 100 with normal pregnancy were studied to measure serum aldosterone and progesterone levels and for the genotypification of the -344T/C polymorphism of CYP11B2 gene and the S810L mutation of MR by RFLP-PCR and SSP, respectively. Serum aldosterone levels were reduced (<0.000001) and serum progesterone levels increased (<0.000001) in gestational hypertensive women as compared with normal pregnant women. The -344T/C of CYP11B2 genotypic frequencies were similar in the hypertensive and normotensive pregnant women. The 810L-mutated allele of MR was found in 12% of the hypertensive and 9.4% of the normotensive pregnant women. In contrast to the observations made in preeclampsia, the genotype of -344T/C of CYP11B2 was neither related with gestational hypertension nor with aldosterone levels at delivery. The frequency of the S810L mutation was similar in the hypertensive and normotensive women but higher than observed in other reports.

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References

  1. Roberts JM, Pearson G, Cutler J, Lindheimer M . Summary of the NHLBI Working Group on research on hypertension during pregnancy. Hypertension 2003; 41: 437–445.

    Article  CAS  Google Scholar 

  2. Pérez-Juárez MP, Castañeda-Sánchez O, Arellano-Cuadros V, Espinosa-Suárez J . Frecuencia de hipertensión arterial inducida por el embarazo en derechohabientes de una unidad de Medicina Familiar de Cd. Obregón Sonora. Arch Med Familiar 2008; 10: 13–16.

    Google Scholar 

  3. Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S . Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Genet 2000; 91: 256–260.

    Article  CAS  Google Scholar 

  4. Chappell S, Morgan L . Searching for genetic clues to the causes of pre-eclampsia. Clin Sci 2006; 110: 443–458.

    Article  CAS  Google Scholar 

  5. Symonds FM, Broughton-Pipkin F, Craven DJ . Changes in the renin-angiotensin system in primigravidae with hypertensive disease of pregnancy. Br J Obstet Gynaecol 1975; 82: 643–650.

    Article  CAS  Google Scholar 

  6. Shojaati K, Causevic M, Kedereit B, Dick B, Imobersteg J, Schneider H et al. Evidence for compromised aldosterone synthase enzyme activity in preeclampsia. Kidney Int 2004; 66: 2322–2328.

    Article  CAS  Google Scholar 

  7. Salas SP, Marshall G, Gutiérrez BL, Rosso R . Time course of maternal plasma volume and hormonal changes in women with preeclampsia or fetal growth restriction. Hypertension 2006; 47: 203–208.

    Article  CAS  Google Scholar 

  8. Oelkers WK . Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids 1996; 61: 166–171.

    Article  CAS  Google Scholar 

  9. Brown MA, Wang J, Whitworth JA . The renin-angiotensin-aldosterone system in pre-eclampsia. Clin Exp Hypertens 1997; 19: 713–726.

    Article  CAS  Google Scholar 

  10. Tsukada K, Ishimitsu T, Teranishi M, Saitoh M, Yoshil M, Inada H et al. Positive association of CYP11B2 gene polymorphism with genetic predisposition to essential hypertension. J Hum Hypertens 2002; 16: 789–793.

    Article  CAS  Google Scholar 

  11. Zhu H, Sagnella GA, Dong Y, Miller MA, Onipinla A, Markandu ND et al. Contrasting association between aldosterone synthase gene polymorphisms and essential hypertension in black and in white. J Hypertens 2003; 21: 87–95.

    Article  CAS  Google Scholar 

  12. Pojoga L, Gautier S, Blanc H, Guyene TT, Poirier O, Cambien F et al. Genetic determination of plasma aldosterone levels in essential hypertension. Am J Hypertens 1998; 11: 856–860.

    Article  CAS  Google Scholar 

  13. Davies E, Holloway CD, Ingram MC, Inglis GC, Friel EC, Morrison C et al. Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension 1999; 33: 703–707.

    Article  CAS  Google Scholar 

  14. Lim PO, MacDonald TM, Holloway CH, Friel E, Anderson NH, Dow E et al. Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio. J Clin Endocrinol Metab 2002; 87: 4398–4402.

    Article  CAS  Google Scholar 

  15. Paillard F, Chansel D, Brand E, Benetos A, Thomas F, Czekalski S et al. Genotype-phenotype relationships for the rennin-angiotensin-aldosterone system in a normal population. Hypertension 1999; 34: 423–429.

    Article  CAS  Google Scholar 

  16. Barbato A, Russo P, Siani A, Folkerd EJ, Miller MA, Venezia A et al. Aldosterone synthase gene (CYP11B2) C-344T polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population. J Hypertens 2004; 22: 1895–1901.

    Article  CAS  Google Scholar 

  17. Casiglia E, Tikhonoff V, Mazza A, Rynkiewicz A, Limon J, Caffi S et al. C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: a population-based study. J Hypertens 2005; 23: 1991–1996.

    Article  CAS  Google Scholar 

  18. Vasconcelos D, Izidoro-Toledo TC, Sandrim VC, Tanus-Santos JE, Palei A, Cavalli RC . Aldosterone synthase gene polymorphism is not associated with gestational hypertension or preeclampsia. Clinica Chimica Acta 2009; 400: 139–141.

    Article  Google Scholar 

  19. Escher G, Cristiano M, Causevic M, Baumann M, Fley FJ, Subek D et al. High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome. Nephrol Dial Transplant 2009; 24: 1870–1875.

    Article  CAS  Google Scholar 

  20. Percin FE, Cetin M, Pinarbasi E, Akgun E, Gurlek F, Cetin A . Lack of association between the CYP11B2 gene polymorphism and preeclampsia, eclampsia, and the HELLP syndrome in Turkish women. Eur J Obstet Gynecol Reprod Biol 2006; 127: 213–217.

    Article  CAS  Google Scholar 

  21. Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A et al. Activation mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 2000; 289: 119–123.

    Article  CAS  Google Scholar 

  22. Schmider-Ross A, Wirsing M, Büscher U, Neitzel H, Krause M, Henrich W et al. Analysis of the S810L point mutation of the mineralocorticoid receptor in patients with pregnancy-induced hypertension. Hypertens Pregnancy 2004; 23: 113–119.

    Article  CAS  Google Scholar 

  23. Kamide K, Yang J, Kokubo Y, Takiuchi S, Niwa Y, Horio T et al. A novel missense mutation, F826Y, in the mineralocorticoid receptor gene in Japanese hypertensives: its implications for clinical phenotypes. Hypertens Res 2005; 28: 703–709.

    Article  CAS  Google Scholar 

  24. Gifford RW, August PA, Cunningham G, Green LA, Lindheimer MD, McNellis D et al. Report of the national high blood pressure education program working group on the high blood pressure in pregnancy. Am J Obstet Gynecol 2000; 183: S1–S22.

    Article  Google Scholar 

  25. Kupari M, Hautanen A, Lankinen L, Koskinen P, Virolainen J, Nikkila H et al. Association between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass and function. Circulation 1998; 97: 567–575.

    Article  Google Scholar 

  26. Portrat-Doyen S, Tourniaire J, Richard O, Mulatero O, Aupetit-Faisant B, Curnow KM et al. Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene. J Clin Endocrinol Metab 1998; 83: 4156–4161.

    CAS  PubMed  Google Scholar 

  27. Myles K, Funder JW . Progesterone binding to mineralocorticoid receptors: in vitro and in vivo studies. Am J Physiol 1996; 270: F601–F607.

    Google Scholar 

  28. Israel A, Peceño A . Renin-angiotensin-aldosterone system in pregnancy-induced hypertension. J Hum Hypertens 2000; 14 (Suppl 1): S36–S39.

    Article  CAS  Google Scholar 

  29. Kim EH, Lim JH, Kim YH, Park YW . The relationship between aldosterone to renin ratio and RI value of the artery in the preeclamptic patient vs normal pregnancy. Yonsei Med J 2008; 49: 138–143.

    Article  Google Scholar 

  30. Miller VM, Vanhoutte PM . Progesterone and modulation of endothelium-dependent responses in canine coronary arteries. Am J Physiol 1991; 261: R1022–R1027.

    CAS  PubMed  Google Scholar 

  31. Farese S, Shojaati K, Kadereit B, Frey FJ, Mohaupt MG . Blood pressure reduction in pregnancy by sodium chloride. Nephrol Dial Transplant 2006; 21: 1984–1987.

    Article  Google Scholar 

  32. Ballesteros-Vasquez MN, Cabrera-Pacheco RM, Saucedo-Tamayo MS, Grijalva-Haro MI . Consumo de fibra dietética, sodio, potasio y calcio y su relación con la presión arterial en hombres adultos normotensos. Salud Pública de México 1998; 40: 241–246.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Sciences, University of Guanajuato, León, Guanajuato, México

    M Ramírez-Salazar, S Zaina, J M Malacara, C Kornhauser & E Pérez-Luque

  2. Mexican Social Security Institute, Gynecology-Pediatry Hospital, Unit 48, León, Guanajuato, México

    G Romero-Gutiérrez

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  1. M Ramírez-Salazar
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Correspondence to E Pérez-Luque.

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Ramírez-Salazar, M., Romero-Gutiérrez, G., Zaina, S. et al. Relationship of aldosterone synthase gene (C-344T) and mineralocorticoid receptor (S810L) polymorphisms with gestational hypertension. J Hum Hypertens 25, 320–326 (2011). https://doi.org/10.1038/jhh.2010.58

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