Skip to main content
SpringerLink
Log in

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant—HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P > 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P > 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

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

  1. Friedman SA, Taylor RN, Roberts JM (1991) Pathophysiology of preeclampsia. Clin Perinatol 18(4):661–682

    PubMed  CAS  Google Scholar 

  2. Reslan OM, Khalil RA (2010) Vitamin D effects on pregnancy and the placenta. Cardiovasc Hematol Agents Med Chem 8(4):204–226

    Article  PubMed  CAS  Google Scholar 

  3. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM (2007) Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 92(9):3517–3522

    Article  PubMed  CAS  Google Scholar 

  4. Urrutia RP, Thorp JM (2012) Vitamin D in pregnancy: current concepts. Curr Opin Obstet Gynecol 24(2):57–64

    Article  PubMed  Google Scholar 

  5. Barth JH, Field HP, Mather AN, Plein S (2012) Serum 25 hydroxy-vitamin D does not exhibit an acute phase reaction after acute myocardial infarction. Ann Clin Biochem 27:27

    Google Scholar 

  6. Cozzolino M, Stucchi A, Rizzo MA, Soldati L, Cusi D, Ciceri P, Brenna I, Elli F, Gallieni M (2012) Vitamin D receptor activation and prevention of arterial ageing. Nutr Metab Cardiovasc Dis 22(7):547–552

    Article  PubMed  CAS  Google Scholar 

  7. Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, Binkley N, Stein JH (2012) A prospective randomized controlled trial of the effects of vitamin d supplementation on cardiovascular disease risk. PLoS One 7(5):7

    Article  Google Scholar 

  8. Pilz S, Kienreich K, Tomaschitz A, Lerchbaum E, Meinitzer A, Marz W, Zittermann A, Dekker JM (2012) Vitamin D and cardiovascular disease: update and outlook. Scand J Clin Lab Invest Suppl 243:83–91

    PubMed  Google Scholar 

  9. Brannon PM (2012) Key questions in vitamin D research. Scand J Clin Lab Invest Suppl 243:154–162

    PubMed  Google Scholar 

  10. Novakovic B, Sibson M, Ng HK, Manuelpillai U, Rakyan V, Down T, Beck S, Fournier T, Evain-Brion D, Dimitriadis E, Craig JM, Morley R, Saffery R (2009) Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface. J Biol Chem 284(22):14838–14848

    Article  PubMed  CAS  Google Scholar 

  11. Bui T, Christin-Maitre S (2011) Vitamin D and pregnancy. Ann Endocrinol 72(1):S23–S28

    Article  Google Scholar 

  12. De-Regil LM, Palacios C, Ansary A, Kulier R, Pena-Rosas JP (2012) Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev 15(2):1–50

    Google Scholar 

  13. Dror DK (2011) Vitamin D status during pregnancy: maternal, fetal, and postnatal outcomes. Curr Opin Obstet Gynecol 23(6):422–426

    Article  PubMed  Google Scholar 

  14. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2):143–156

    Article  PubMed  CAS  Google Scholar 

  15. Falleti E, Bitetto D, Fabris C, Fattovich G, Cussigh A, Cmet S, Ceriani E, Fornasiere E, Pasino M, Ieluzzi D, Pirisi M, Toniutto P (2012) Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C. Hepatology 18(10):25848

    Google Scholar 

  16. Jorde R, Schirmer H, Wilsgaard T, Joakimsen RM, Mathiesen EB, Njolstad I, Lochen ML, Figenschau Y, Berg JP, Svartberg J, Grimnes G (2012) Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The tromso study. PLoS One 7(5):23

    Article  Google Scholar 

  17. Santos BR, Mascarenhas LP, Satler F, Boguszewski MC, Spritzer PM (2012) Vitamin D deficiency in girls from South Brazil: a cross-sectional study on prevalence and association with vitamin D receptor gene variants. BMC Pediatr 12(1):62

    Article  PubMed  Google Scholar 

  18. Tantawy AA, El Bostany EA, Matter RM, El Ghoroury EA, Ragab S, El Sherif NH (2012) Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: relation to corticosteroid therapy and vitamin D receptor gene polymorphisms. Platelets 6:6

    Google Scholar 

  19. Vuolo L, Di Somma C, Faggiano A, Colao A (2012) Vitamin D and cancer. Front Endocrinol 3(58):23

    Google Scholar 

  20. Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA (2004) Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. J Steroid Biochem Mol Biol 89–90(1–5):187–193

    Article  PubMed  Google Scholar 

  21. Sandrim VC, Palei AC, Cavalli RC, Araujo FM, Ramos ES, Duarte G, Tanus-Santos JE (2008) eNOS haplotypes associated with gestational hypertension or preeclampsia. Pharmacogenomics 9(10):1467–1473

    Article  PubMed  CAS  Google Scholar 

  22. Sandrim VC, Palei AC, Luizon MR, Izidoro-Toledo TC, Cavalli RC, Tanus-Santos JE (2010) eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension. Pharmacogenomics J 10(1):40–45

    Article  PubMed  CAS  Google Scholar 

  23. Palei AC, Sandrim VC, Duarte G, Cavalli RC, Gerlach RF, Tanus-Santos JE (2010) Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension. Clin Chim Acta 411(11–12):874–877

    Article  PubMed  CAS  Google Scholar 

  24. Sandrim VC, Palei AC, Cavalli RC, Araujo FM, Ramos ES, Duarte G, Tanus-Santos JE (2009) Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension. Mol Hum Reprod 15(2):115–120

    Article  PubMed  CAS  Google Scholar 

  25. Palei AC, Sandrim VC, Amaral LM, Machado JS, Cavalli RC, Duarte G, Tanus-Santos JE (2012) Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy. Exp Mol Pathol 92(2):217–221

    Article  PubMed  CAS  Google Scholar 

  26. Rezende VB, Barbosa F Jr, Montenegro MF, Sandrim VC, Gerlach RF, Tanus-Santos JE (2007) An interethnic comparison of the distribution of vitamin D receptor genotypes and haplotypes. Clin Chim Acta 384(1–2):155–159

    Article  PubMed  CAS  Google Scholar 

  27. Rezende VB, Barbosa F Jr, Montenegro MF, Sandrim VC, Gerlach RF, Tanus-Santos JE (2008) Haplotypes of vitamin D receptor modulate the circulating levels of lead in exposed subjects. Arch Toxicol 82(1):29–36

    Article  PubMed  CAS  Google Scholar 

  28. Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68(4):978–989

    Article  PubMed  CAS  Google Scholar 

  29. Brannon PM (2012) Vitamin D and adverse pregnancy outcomes: beyond bone health and growth. Proc Nutr Soc 71(2):205–212

    Article  PubMed  CAS  Google Scholar 

  30. Wuerzner G, Burnier M, Waeber B (2012) Should hypertensive patients take vitamin D? Curr Hypertens Rep 22:22

    Google Scholar 

  31. Roberts JM, Cooper DW (2001) Pathogenesis and genetics of pre-eclampsia. Lancet 357(9249):53–56

    Article  PubMed  CAS  Google Scholar 

  32. Robertson SA, Bromfield JJ, Tremellen KP (2003) Seminal ‘priming’ for protection from pre-eclampsia-a unifying hypothesis. J Reprod Immunol 59(2):253–265

    Article  PubMed  Google Scholar 

  33. Walker JJ (2000) Pre-eclampsia. Lancet 356(9237):1260–1265

    Article  PubMed  CAS  Google Scholar 

  34. Weisman Y, Harell A, Edelstein S, David M, Spirer Z, Golander A (1979) 1 alpha, 25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in vitro synthesis by human decidua and placenta. Nature 281(5729):317–319

    Article  PubMed  CAS  Google Scholar 

  35. Pilz S, Tomaschitz A (2010) Role of vitamin D in arterial hypertension. Expert Rev Cardiovasc Ther 8(11):1599–1608

    Article  PubMed  CAS  Google Scholar 

  36. Swapna N, Vamsi UM, Usha G, Padma T (2011) Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension. Indian J Hum Genet 17(3):201–206

    Article  PubMed  CAS  Google Scholar 

  37. Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12(6):915–921

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was funded by Fundação de Amparo `a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirao Preto, SP, CEP 14049-900, Brazil

    Vania B. Rezende, Lorena Machado & Jose E. Tanus-Santos

  2. Núcleo de Pós-Graduação e Pesquisa, Santa Casa de Belo Horizonte, Av. Francisco Sales, 1111, Belo Horizonte, MG, Brazil

    Valeria C. Sandrim

  3. Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, R. Tessália Vieira de Camargo, 126, Campinas, SP, 13083-887, Brazil

    Ana C. Palei

  4. Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, Monte Alegre, Ribeirao Preto, SP, CEP 14049-900, Brazil

    Ricardo C. Cavalli & Geraldo Duarte

Authors
  1. Vania B. Rezende
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valeria C. Sandrim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana C. Palei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lorena Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ricardo C. Cavalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Geraldo Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jose E. Tanus-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jose E. Tanus-Santos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rezende, V.B., Sandrim, V.C., Palei, A.C. et al. Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy. Mol Biol Rep 39, 10903–10906 (2012). https://doi.org/10.1007/s11033-012-1988-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1988-y

Keywords

Search

Navigation