American Journal of Obstetrics & Gynecology
Volume 202, Issue 5 , Pages 445.e1-445.e11 , May 2010

Allelic variations in angiogenic pathway genes are associated with preeclampsia

Presented orally at the 30th Annual Meeting of the Society for Maternal-Fetal Medicine, Chicago, IL, Feb. 1-6, 2010. The racing flag logo above indicates that this article was rushed to press for the benefit of the scientific community.

  • Sindhu K. Srinivas, MD, MSCE

      Affiliations

    • Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA
    • ,
  • Alanna C. Morrison, PhD

      Affiliations

    • Human Genetics Center and Division of Epidemiology and Disease Control, University of Texas Health Science Center at Houston, Houston, TX
    • ,
  • Christina M. Andrela, MS

      Affiliations

    • Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA
    • ,
  • Michal A. Elovitz, MD

      Affiliations

    • Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA

Received 23 November 2009 ,Revised 29 December 2009 ,Accepted 15 January 2010.

References 

  1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785–799
  2. Centers for Disease Control. Morbidity and mortality weekly report: pregnancy-related mortality surveillance—United States, 1991–1999. CDC MMWR. 2003;52:SS-2
  3. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357:53–56
  4. Wang Y, Gu Y, Zhang Y, Lewis DF. Evidence of endothelial dysfunction in preeclampsia: decreased endothelial nitric oxide synthase expression is associated with increased cell permeability in endothelial cells from preeclampsia. Am J Obstet Gynecol. 2004;190:817–824
  5. Redman CW. Current topic: pre-eclampsia and the placenta. Placenta. 1991;12:301–308
  6. Robertson SA, Ingman WV, O'Leary S, Sharkey DJ, Tremellen KP. Transforming growth factor beta: a mediator of immune deviation in seminal plasma. J Reprod Immunol. 2002;57:109–128
  7. Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999;180:499–506
  8. Catov JM, Ness RB, Kip KE, Olsen J. Risk of early or severe pre-eclampsia related to pre-existing conditions. Int J Epidemiol. 2007;36:412–419
  9. Bodnar LM, Ness RB, Markovic N, Roberts JM. The risk of preeclampsia rises with increasing prepregnancy body mass index. Ann Epidemiol. 2005;15:475–482
  10. Diagnosis and management of preeclampsia and eclampsia. In: American College of Obstetricians and Gynecologists Compendium 2008: practice bulletin, no. 33;2002;2002.
  11. Campbell DM, MacGillivray I, Carr-Hill R. Pre-eclampsia in second pregnancy. BJOG. 1985;92:131–140
  12. Dildy GA, Belfort MA, Smulian JC. Preeclampsia recurrence and prevention. Semin Perinatol. 2007;31:135–141
  13. Cnattingius S, Reilly M, Pawitan Y, Lichtenstein P. Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study. Am J Med Genet A. 2004;130A:365–371
  14. Dawson LM, Parfrey PS, Hefferton D, et al. Familial risk of preeclampsia in Newfoundland: a population-based study. J Am Soc Nephrol. 2002;13:1901–1906
  15. Ness RB, Markovic N, Bass D, Harger G, Roberts JM. Family history of hypertension, heart disease, and stroke among women who develop hypertension in pregnancy. Obstet Gynecol. 2003;102:1366–1371
  16. Lachmeijer A, Dekker G, Pals G, Aarnoudse J, Kate L, Arngrimsson R. Searching for preeclampsia genes: the current position. Eur J Obstet Gynecol Reprod Biol. 2002;105:94–113
  17. Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350:672–683
  18. Salahuddin S, Lee Y, Vadnais M, Sachs BP, Karumanchi SA, Lim KH. Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases of pregnancy. Am J Obstet Gynecol. 2007;197:28.e1-6
  19. Rana S, Karumanchi SA, Levine RJ, et al. Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia. Hypertension. 2007;50:137–142
  20. Moore Simas TA, Crawford SL, Solitro MJ, Frost SC, Meyer BA, Maynard SE. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am J Obstet Gynecol. 2007;197:244.e1-8
  21. Romero R, Nien JK, Espinoza J, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med. 2008;21:9–23
  22. Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355:992–1005
  23. Edlow A, Srinivas S, Elovitz M. Investigating the risk of hypertension shortly after pregnancies complicated by preeclampsia. Am J Obstet Gynecol. 2009;200:e60–e62
  24. Mazar R, Srinivas S, Sammel M, Andrela C, Elovitz M. Metabolic score as a novel approach to assessing preeclampsia risk. Am J Obstet Gynecol. 2007;197:411.e1-5
  25. Srinivas SK, Edlow AG, Neff PM, Sammel MD, Andrela CM, Elovitz MA. Rethinking IUGR in preeclampsia: dependent or independent of maternal hypertension. J Perinatol. 2009;29:680–684
  26. Srinivas SK, Sammel MD, Bastek J, et al. Evaluating the association between all components of the metabolic syndrome and pre-eclampsia. J Matern Fetal Neonatal Med. 2009;22:501–509
  27. Keating B, Tischfield S, Murray S, et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. PLoS One. 2008;3:e3583
  28. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–575
  29. Excoffier L, Slatkin M. Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol. 1995;12:921–927
  30. Mathias RA, Gao P, Goldstein JL, et al. A graphical assessment of p-values from sliding window haplotype tests of association to identify asthma susceptibility loci on chromosome 11q. BMC Genet. 2006;7:38
  31. Shibata E, Rajakumar A, Powers RW, et al. Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor. J Clin Endocrinol Metab. 2005;90:4895–4903
  32. McKeeman GC, Ardill JE, Caldwell CM, Hunter AJ, McClure N. Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop. Am J Obstet Gynecol. 2004;191:1240–1246
  33. Chedraui P, Lockwood CJ, Schatz F, et al. Increased plasma soluble fms-like tyrosine kinase 1 and endoglin levels in pregnancies complicated with preeclampsia. J Matern Fetal Neonatal Med. 2009;565–570
  34. Rogers MS, D'Amato RJ. The effect of genetic diversity on angiogenesis. Exp Cell Res. 2006;312:561–574
  35. Papazoglou D, Galazios G, Koukourakis MI, et al. Vascular endothelial growth factor gene polymorphisms and pre-eclampsia. Mol Hum Reprod. 2004;10:321–324
  36. Sitras V, Paulssen RH, Gronaas H, et al. Differential placental gene expression in severe preeclampsia. Placenta. 2009;30:424–433
  37. Kim SY, Lim JH, Yang JH, et al. Dinucleotide repeat polymorphism in Fms-like tyrosine kinase-1 (Flt-1) gene is not associated with preeclampsia. BMC Med Genet. 2008;9:68

 Supported in part by Grant no. K12HD001265 (S.K.S.) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, and by the University Research Foundation, University of Pennsylvania.

 Cite this article as: Srinivas SK, Morrison AC, Andrela CM, et al. Allelic variations in angiogenic pathway genes are associated with preeclampsia. Am J Obstet Gynecol 2010;202:445.e1-11.

 Reprints not available from the authors.

PII: S0002-9378(10)00070-0

doi: 10.1016/j.ajog.2010.01.040

American Journal of Obstetrics & Gynecology
Volume 202, Issue 5 , Pages 445.e1-445.e11 , May 2010

Article Tools

* Image Usage & Resolution