Archives of Gynecology and Obstetrics

, Volume 291, Issue 5, pp 1029–1035 | Cite as

Investigation of polymorphisms in pre-eclampsia related genes VEGF and IL1A

  • Vanessa Resende Souza Silva
  • Fernanda Caroline Soardi
  • Sarah Cristina Sato Vaz Tanaka
  • Roseane Lopes da Silva-Grecco
  • Marina Carvalho Paschoini
  • Marly Aparecida Spadotto Balarin
Maternal-Fetal Medicine
First Online:
Received:
Accepted:

Abstract

Introduction

Pre-eclampsia (PE) is a pregnancy-specific multisystemic syndrome characterized by high blood pressure and presence of protein in the urine. The pathogenesis of pre-eclampsia is poorly understood and many factors such as environment, genetic, and immunology may be involved in PE pathophysiology. Among the genetic factors, there is an association between pre-eclampsia and polymorphisms in some genes of different population samples, as vascular endothelial growth factor and interleukin 1 alpha. The vascular endothelial growth factor gene is highly polymorphic and acts as a regulator in endothelial cell proliferation and vascular permeability. The secretion of interleukin 1 alpha leads to a pro-inflammatory cascade, which leads to high levels of circulating cytokines. This high amount of cytokines corroborates to structural and functional alterations in endothelial cells. The aim of this study was to investigate the vascular endothelial growth factor (VEGF) G-634C and interleukin 1 alpha (IL1A) rs3783550 polymorphism in a specific Brazilian pre-eclampsia group.

Material and Methods

The evaluation of the vascular endothelial growth factor polymorphism was performed by PCR–RFLP restriction enzyme BsmFI and the IL1A polymorphism by allele-specific PCR. Molecular investigation was carried out by fragment size analysis on agarose and/or polyacrylamide gels.

Results

However, no relation between polymorphism VEGF G-634C and pre-eclampsia was observed, indicating that further investigations with a larger sampling and other polymorphisms are still required. On the other hand, the rs3783550 polymorphism in the interleukin 1 alpha gene is correlated to pre-eclampsia, indicating that women with the allele A have a higher probability of developing the disease.

Conclusion

Thus, the interleukin 1 alpha gene could be used as a therapeutic tool for the diagnosis, as well as for monitoring the patients.

Keywords

Pre-eclampsia VEGF IL1A Polymorphisms 
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Notes

Acknowledgments

Research supported by FAPEMIG (No. CBB\APQ 00838-11) and Fundação de Pesquisa e Pesquisa de Uberaba–FUNEPU.

Conflict of interest

We declare that we have no conflict of interest.

References

  1. 1.
    Laurenti R, Jorge MHPM, Gotlieb SLD (2004) A mortalidade materna nas capitais brasileiras: algumas características e estimativa de um fator de ajuste. Rev Bras Epidemiol 7:449–460CrossRefGoogle Scholar
  2. 2.
    Polsani S, Phipps E, Jim B (2013) Emerging new biomarkers of preeclampsia. Adv Chronic Kidney Dis 20(3):271–279. doi: 10.1053/j.ackd.2013.01.001 CrossRefGoogle Scholar
  3. 3.
    Saftlas AF, Olson DR, Franks AL, Atrash HK, Pokras R (1990) Epidemiology of preeclampsia and eclampsia in the United States, 1979-1986. Am J Obstet Gynecol 163(2):460–465CrossRefPubMedGoogle Scholar
  4. 4.
    Winn VD, Gormley M, Paquet AC, Kjaer-Sorensen K, Kramer A, Rumer KK, Haimov-Kochman R, Yeh RF, Overgaard MT, Varki A, Oxvig C, Fisher SJ (2009) Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2. Endocrinology 150(1):452–462. doi: 10.1210/en.2008-0990 CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Chambers JC, Fusi L, Malik IS, Haskard DO, De Swiet M, Kooner JS (2001) Association of maternalendothelial dysfunction with preeclampsia. JAMA 285(12):1607–1612CrossRefPubMedGoogle Scholar
  6. 6.
    Noris M, Perico N, Remuzzi G (2005) Mechanisms of disease: preeclampsia. Nat Clin Pract Nephrol 1(2):98–114 (Review)CrossRefPubMedGoogle Scholar
  7. 7.
    Barton JR, Sibai BM (2008) Prediction and prevention of preeclampsia. Obstet Gynecol 112:359–372. doi: 10.1097/AOG.0b013e3181801d56 (Review)CrossRefPubMedGoogle Scholar
  8. 8.
    Dekker G, Robillard PY, Roberts C (2011) The etiology of preeclampsia: the role of the father. J Reprod Immunol 89(2):126–132. doi: 10.1016/j.jri.2010.12.010 CrossRefPubMedGoogle Scholar
  9. 9.
    Benjamin F, Craig CJ (1961) Uterine distension and pre-eclamptic toxaemia. J Obstet Gynaecol Br Emp 68:827–830CrossRefPubMedGoogle Scholar
  10. 10.
    Robertson WB, Brosens I, Landells WN (1985) Abnormal placentation. Obstet Gynecol Annu 14:411–426PubMedGoogle Scholar
  11. 11.
    Terao T, Maki M, Ikenoue T, Gotoh K, Murata M, Iwasaki H, Shibata J, Nakabayashi M, Muraoka M, Takeda Y et al (1991) The relationship between clinical signs and hypercoagulable state in toxemia of pregnancy. Gynecol Obstet Invest 31(2):74–85CrossRefPubMedGoogle Scholar
  12. 12.
    Dekker GA, Sibai BM (1998) Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 179(5):1359–1375 (Review)CrossRefPubMedGoogle Scholar
  13. 13.
    Higgins JR, Brennecke SP (1998) Pre-eclampsia—still a disease of theories? Curr Opin Obstet Gynecol 10(2):129–133 (Review)CrossRefPubMedGoogle Scholar
  14. 14.
    Redman CW, Sacks GP, Sargent IL (1999) Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 180(2 Pt 1):499–506CrossRefPubMedGoogle Scholar
  15. 15.
    Faas MM, Schuiling GA (2001) Pre-eclampsia and the inflammatory response. Eur J Obstet Gynecol Reprod Biol 95(2):213–217 (Review)CrossRefPubMedGoogle Scholar
  16. 16.
    Kupferminc MJ (2003) Thrombophilia and pregnancy. Reprod Biol Endocrinol 14(1):111CrossRefGoogle Scholar
  17. 17.
    Fisher SJ (2004) The placental problem: linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia. Reprod Biol Endocrinol 2:53. doi: 10.1186/1477-7827-2-53 CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Myatt L, Cui X (2004) Oxidative stress in the placenta. Histochem Cell Biol 122(4):369–382 (Review)CrossRefPubMedGoogle Scholar
  19. 19.
    Shah DM (2005) Role of the renin-angiotensin system in the pathogenesis of preeclampsia. Am J Physiol Renal Physiol 288(4):F614–F625CrossRefPubMedGoogle Scholar
  20. 20.
    Conrad KP, Benyo DF (1997) Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol 37(3):240–249 (Review)CrossRefPubMedGoogle Scholar
  21. 21.
    Redman CW, Sargent IL (2009) Placental stress and preeclampsia: a revised view. Placenta 30(Suppl)A:S38–S42. doi: 10.1016/j.placenta.2008.11.021 CrossRefGoogle Scholar
  22. 22.
    Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S et al (1993) A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 4(1):59–61CrossRefPubMedGoogle Scholar
  23. 23.
    Chen G, Wilson R, Wang SH, Zheng HZ, Walker JJ, Mckillop JH (1996) Tumor necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia. Clin Exp Immunol 104(1):154–159CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Grandone E, Margaglione M, Colaizzo D, Cappucci G, Paladini D, Martinelli P, Montanaro S, Pavone G, Di Minno G (1997) Factor V Leiden, C > T MTHFR polymorphism and genetic susceptibility to preeclampsia. Thromb Haemost 77(6):1052–1054PubMedGoogle Scholar
  25. 25.
    Laivuori H, Kaaja R, Ylikorkala O, Hiltunen T, Kontula K (2000) 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene and preeclampsia. Obstet Gynecol 96(2):277–280CrossRefPubMedGoogle Scholar
  26. 26.
    Huber A, Grimm C, Jirecek S, Zeillinger R, Husslein P, Hefler L (2005) Polymorphisms within the interleukin-1 gene family and unexplained late intrauterine fetal death: a multi-center study. Am J Reprod Immunol 53(3):132–135CrossRefPubMedGoogle Scholar
  27. 27.
    Chappell S, Morgan L (2006) Searching for genetic clues to the causes of preeclampsia. Clin Sci (Lond) 110(4):443–458CrossRefGoogle Scholar
  28. 28.
    Ferrara N, Henzel WJ (2012) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 425(3):540–547. doi: 10.1016/j.bbrc.2012.08.02 CrossRefPubMedGoogle Scholar
  29. 29.
    Papapetropoulos A, García-Cardeña G, Madri JA, Sessa WC (1997) Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100(12):3131–3139CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Vincenti V, Cassano C, Rocchi M, Persico G (1996) Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation 93(8):1493–1495CrossRefPubMedGoogle Scholar
  31. 31.
    Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF (2000) Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest 106(11):1311–1319CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Papazoglou D, Galazios G, Koukourakis MI, Panagopoulos I, Kontomanolis EN, Papatheodorou K, Maltezos E (2004) Vascular endothelial growth factor gene polymorphisms and pré-eclampsia. Mol Hum Reprod 10(5):321–324CrossRefPubMedGoogle Scholar
  33. 33.
    Bányász I, Szabó S, Bokodi G, Vannay A, Vásárhelyi B, Szabó A, Tulassay T, Rigó J Jr (2006) Genetic polymorphisms of vascular endothelial growth factor in severe pré-eclampsia V. Mol Hum Reprod 12(4):233–236CrossRefPubMedGoogle Scholar
  34. 34.
    Shim JY, Jun JK, Jung BK, Kim SH, Won HS, Lee PR, Kim A (2007) Vascular endothelial growth factor gene +936 C/T polymorphism is associated with preeclampsia in Korean women. Am J Obstet Gynecol 197(3):271CrossRefPubMedGoogle Scholar
  35. 35.
    Sandrim VC, Palei AC, Cavalli RC, Araújo FM, Ramos ES, Duarte G, Tanus-Santos JE (2009) Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestacional hypertension. Mol Hum Reprod 15(2):115–120. doi: 10.1093/molehr/gan076 CrossRefPubMedGoogle Scholar
  36. 36.
    Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K, Inoue I, Katayama S (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51(5):1635–1639CrossRefPubMedGoogle Scholar
  37. 37.
    Cotran RS, Pober JS (1990) Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. J Am Soc Nephrol 1(3):225–235PubMedGoogle Scholar
  38. 38.
    Pober JS, Cotran RS (1990) Cytokines and endothelial cell biology. Physiol Rev 70(2):427–451 (Review)PubMedGoogle Scholar
  39. 39.
    Dinarello CA (1998) Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 16(5–6):457–499 (Review)CrossRefPubMedGoogle Scholar
  40. 40.
    Goddard KA, Tromp G, Romero R, Olson JM, Lu Q, Xu Z, Parimi N, Nien JK, Gomez R, Behnke E, Solari M, Espinoza J, Santolaya J, Chaiworapongsa T, Lenk GM, Volkenant K, Anant MK, Salisbury BA, Carr J, Lee MS, Vovis GF, Kuivaniemi H (2007) Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes. Hum Hered 63(1):1–16CrossRefPubMedGoogle Scholar
  41. 41.
    Sambrook J, Fritsch EF, Maniatis TE (1989) Molecular cloning, a laboratory manual. Cold Spring Harbor, New YorkGoogle Scholar
  42. 42.
    Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191CrossRefPubMedGoogle Scholar
  43. 43.
    Cnattingius S, Reilly M, Pawitan Y, Lichtenstein P (2004) Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study. Am J Med Genet A 130A(4):365–371CrossRefPubMedGoogle Scholar
  44. 44.
    Staines-Urias E, Paez MC, Doyle P, Dudbridge F, Serrano NC, Ioannidis JP, Keating BJ, Hingorani AD, Casas JP (2012) Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis. Int J Epidemiol 41(6):1764–1775. doi: 10.1093/ije/dys162 CrossRefPubMedGoogle Scholar
  45. 45.
    Luizon MR, Sandrim VC, Palei AC, Lacchini R, Cavalli RC, Duarte G, Tanus-Santos JE (2012) Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy. Hypertens Res 35(9):917–921. doi: 10.1038/hr.2012.60 CrossRefPubMedGoogle Scholar
  46. 46.
    Chedraui P, Solis EJ, Bocci G, Gopal S, Russo E, Escobar GS, Hidalgo L, Pérez-López FR, Genazzani AR, Mannella P, Simoncini T (2013) Feto-placental nitric oxide, asymmetric dimethylarginine and vascular endothelial growth factor (VEGF) levels and VEGF gene polymorphisms in severe preeclampsia. J Matern Fetal Neonatal Med 26(3):226–232. doi: 10.3109/14767058.2012.733760 CrossRefPubMedGoogle Scholar
  47. 47.
    Cunha VM, Grecco RL, Paschoini MC, Silva SR, Ruiz MT, Balarin MA (2011) Genetic polymorphisms of vascular endothelial growth factor in preeclampsia. Rev Bras Ginecol Obstet 33(7):158–163CrossRefPubMedGoogle Scholar
  48. 48.
    Darmochwal-Kolarz D, Rolinski J, Leszczynska-Goarzelak B, Oleszczuk J (2002) The expressions of intracellular cytokines in the lymphocytes of preeclamptic patients. Am J Reprod Immunol 48(6):381–386CrossRefPubMedGoogle Scholar
  49. 49.
    Li J, Liu M, Zong J, Tan P, Wang J, Wang X, Ye Y, Liu S, Liu X (2014) Genetics variations in IL1A and IL1RN are associated with the risk of preeclampsia in Chinese Han population. Sci Rep 4:5250. doi: 10.1038/screp05250 PubMedCentralPubMedGoogle Scholar
  50. 50.
    Haggerty CL, Ferrell RE, Hubel CA, Markovic N, Harger G, Ness RB (2005) Association between allelic variants in cytokine genes and preeclampsia. Am J Obstet Gynecol 193(1):209–215CrossRefPubMedGoogle Scholar
  51. 51.
    Faisel F, Romppanen EL, Hiltunen M, Helisalmi S, Punnonen K, Salonen J, Heinonen S (2003) Polymorphism in the interleukin 1 receptor antagonist gene in women with preeclampsia. J Reprod Immunol 60(1):61–70CrossRefPubMedGoogle Scholar
  52. 52.
    Hefler LA, Tempfer CB, Gregg AR (2001) Polymorphisms within the interleukin-1 beta gene cluster and pre-eclampsia. Obstet Gynecol 97(5 Pt 1):664–668CrossRefPubMedGoogle Scholar
  53. 53.
    Combarros O, Infante J, Llorca J, Peña N, Fernández-Viadero C, Berciano J (2005) Interaction between interleukin-6 and intercellular adhesion molecule-1 genes and Alzheimer’s disease risk. J Neurol 252(4):485–487CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Vanessa Resende Souza Silva
    • 1
  • Fernanda Caroline Soardi
    • 1
    • 2
  • Sarah Cristina Sato Vaz Tanaka
    • 1
  • Roseane Lopes da Silva-Grecco
    • 1
  • Marina Carvalho Paschoini
    • 3
  • Marly Aparecida Spadotto Balarin
    • 1
  1. 1.Disciplina de Genética, Instituto de Ciências Biológicas e NaturaisUniversidade Federal do Triângulo MineiroUberabaBrazil
  2. 2.Laboratório de Genética Molecular HumanaCBMEG-UNICAMPCampinasBrazil
  3. 3.Departamento Materno-Infantil, Instituto de Ciências da SaudeUFTMUberabaBrazil

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