Candidate Gene, Genome-Wide Association and Bioinformatic Studies in Pre-eclampsia: a Review

  • Semone ThakoordeenEmail author
  • Jagidesa Moodley
  • Thajasvarie Naicker
Preeclampsia (VD Garovic, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Preeclampsia


Purpose of Review

Regardless of the familial linkage reported in pre-eclampsia development, understanding the polymorphic genes associated with pre-eclampsia remains limited. Hence, this review aims to outline the main genetic factors that have been investigated in respect to pre-eclampsia development.

Recent Findings

It is apparent that different genes show significance in varying populations. Notably, it is reported that apolipoprotein-1 gene polymorphisms are associated with pre-eclampsia development in an African-American population, which may be worthwhile to investigate in a Black South African cohort.


Despite the research attention that is focused on this surreptitious syndrome, a definitive cause eludes scientists and physicians, alike. Genetic studies can fulfil a dual purpose of suggesting novel hypotheses through genome-wide screening and testing these hypotheses via candidate gene studies. However, publications to date have only presented inconsistent and conflicting results regarding candidate gene analysis.


Pre-eclampsia Candidate gene studies Genome-wide association studies Bioinformatic studies Apol-1 gene polymorphisms 


Compliance with Ethics Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    •• Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018. This article provides the current classification of hypertensive disorders in pregnancy such as pre-eclampsia.CrossRefPubMedGoogle Scholar
  2. 2.
    Gathiram P, Moodley J. Pre-eclampsia: its pathogenesis and pathophysiology. Cardiovasc J Afr. 2016;27:71–8. Scholar
  3. 3.
    Varnier N, Brownc MA, Reynolds M, Pettit F, Davis G, Mangos G, et al. Indications for delivery in pre-eclampsia. Pregnancy Hypertens. 2018;11:12–7. Scholar
  4. 4.
    WHO. Make every mother and child count, in The world health report 2005. Geneva: World Health Organization; 2005.Google Scholar
  5. 5.
    Jain R, Bindal J. Maternal and perinatal outcomes in eclampsia: a retrospective analysis in a referral hospital. Int J Reprod Contracept Obstet Gynecol. 2017;6(7):2806–11. Scholar
  6. 6.
    Maher GM, O'Keeffe GW, Kenny LC, Kearney PM, Dinan TG, Khashan AS. Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol. BMJ Open. 2017;7:1–5.CrossRefGoogle Scholar
  7. 7.
    • Republic of South Africa. Department of Health. Saving mothers 2014–2016: seventh triennial report on confidential enquiries into maternal deaths in South Africa: executive summary. National Department of Health; 2014–2016. This report provides the current morbidity and mortality rates of mothers and babies in South Africa.Google Scholar
  8. 8.
    Valenzuela FJ, Perez-Sepulveda A, Torres MJ, Correa P, Repetto GM, Illanes SE. Pathogenesis of pre-eclampsia: the genetic component. J Pregnancy. 2012;2012:1–8. Scholar
  9. 9.
    Foidart JM, Schaaps TP, Chantraine F, Munaut C, Lorquet S. Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia—a step forward but not the definitive answer. J Reprod Immunol. 2009;1–6.Google Scholar
  10. 10.
    Thakoordeen S, Moodley J, Naicker T. Serum levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 in HIV associated preeclampsia. Hypertens. Pregnancy. 2017;36(2):168–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Granger JP, Alexander BT, Llinas MT, Bennett WA, Khalil RA. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension. 2001;38:718–22. Scholar
  12. 12.
    Chambers JC, Fusi L, Malik IS, Haskard DO, De Swiet M, Kooner JS. Association of maternal endothelial dysfunction with preeclampsia. JAMA. 2001;285:1607–12. Scholar
  13. 13.
    Cudihy D, Lee RV. The pathophysiology of pre-eclampsia: current clinical concepts. J Obstet Gynaecol. 2009;29(7):576–82. Scholar
  14. 14.
    Herzog EM, Eggink AJ, Willemsen SP, Slieker RC, Wijnands KPJ, Felix JF, et al. Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn. Placenta. 2017;58:122–32. Scholar
  15. 15.
    Haram K, Mortensen JH, Nagy B. Genetic aspects of preeclampsia and the HELLP syndrome. J Pregnancy. 2014;2014:1–14. Scholar
  16. 16.
    Goddard KAB, Tromp G, Romero R, Olson JM, Lu Q, Xu Z, et al. Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes. Hum Hered. 2017;63:1–16.CrossRefGoogle Scholar
  17. 17.
    Chappell S, Morgan L. Searching for genetic clues to the causes of pre-eclampsia. Clin Sci. 2006;110:443–58. Scholar
  18. 18.
    Daher S, Sass N, Olivera LG, Mattar R. Cytokine genotyping in preeclampsia. Am J Reprod Immunol. 2006;55:130–5. Scholar
  19. 19.
    Kamali-Sarvestani E, Kiany S, Gharesi-Fard B, Rabali M. Association study of IL-10 and IFN-γ gene polymorphisms in Iranian women with preeclampsia. Am J Reprod Immunol. 2006;72(1–2):118–26.CrossRefGoogle Scholar
  20. 20.
    Vural P, Degirmencioglu S, Saral N, Demirkan A, Akgul C, Yildirim G, et al. Tumor necrosis factor α, interleukin-6 and interleukin-10 polymorphisms in preeclampsia. J Obstet Gynaecol Res. 2010;36:64–71. Scholar
  21. 21.
    Pinheiro MB, Gomes KB, Ronda CRSC, Guimaraes GG, Freitas LG, Teixeira-Carvalho A, et al. Severe preeclampsia: association of genes polymorphisms and maternal cytokines production in Brazilian population. Cytokine. 2015;71:232–7. Scholar
  22. 22.
    Chen G, Wilson R, Wang SH, Zheng HZ, Walker JJ, Mckillop JHC. Tumour necrosis factor-alpha (TNF-α) gene polymorphism and expression in pre-eclampsia. Clin Exp Immunol. 1996;104(1):154–9. Scholar
  23. 23.
    Mohajertehran F, Afshari JT, Rezaieyazdi Z, Ghomian N. Association of single nucleotide polymorphisms in the human tumor necrosis factor-α and interleukin 1-β genes in patients with pre-eclampsia. Iran J Allergy Asthma Immunol. 2012;11(3):224–9.PubMedGoogle Scholar
  24. 24.
    Shao B, Jiang S, Muyiduli X, Wang S, Mo M, Li M, Wang Z, Yu Y. Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women. Clin Nutr. 2017.
  25. 25.
    Luizon MR, Sandrim VC, Palei ACT, Lacchini R, Cavalli RC, Duarte G, et al. Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy. Hypertens Res. 2012;35:917–21. Scholar
  26. 26.
    Sun C, Zhang Q, Hu B, Zhang K. Investigation of the association between matrix metalloproteinase-9 genetic polymorphisms and development of pre-eclampsia in Chinese pregnant women. Genet Mol Res. 2016;15(3):1–6.Google Scholar
  27. 27.
    Srinivas SK, Morrison AC, Andnela CM, Elovitz MA. Allelic variations in angiogenic pathway genes are associated with preeclampsia. AJOG. 2010;202(5):445.e1–445.e11.CrossRefGoogle Scholar
  28. 28.
    Bouba I, Makrydimas G, Kalaitzidis R, Lolis DE, Siamopoulous KC, Georgiou I. Interaction between the polymorphisms of the renin–angiotensin system in preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2003;110(1):8–11. Scholar
  29. 29.
    Aung M, Konoshita T, Moodley J, Gathiram P. Association of gene polymorphisms of four components of renin-angiotensin-aldosterone system and preeclampsia in South African black women. BJOG. 2017;215:180–7.Google Scholar
  30. 30.
    Rahini Z, Aghaei A, Vaisi-Raygani A. AT2R − 1332 G: a polymorphism and its interaction with AT1R 1166 A: C, ACE I/D and MMP-9 − 1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia. Gene. 2014;538(1):176–81. Scholar
  31. 31.
    Bhatnagar S, Bhattacharjee J, Vaid M, Madan T, Trivedi SS, Sarma PU. Inducible nitric oxide synthase (iNOS) gene polymorphism in pre-eclampsia: a pilot study in North India. Aust N Z J Obstet Gynaecol. 2007;47:477–82. Scholar
  32. 32.
    Chen MX, Yuan ZH, Shan KR. Association of Apolipoprotein J Gene 866C→T polymorphism with preeclampsia and essential hypertension. Gynecol Obstet Investig. 2005;60:13–8.CrossRefGoogle Scholar
  33. 33.
    Tan CY, Ho JFV, Chong YS, Longanath A, Chan YH, Ravichandran J, et al. Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies. Mol Hum Reprod. 2008;14(5):317–24.CrossRefPubMedGoogle Scholar
  34. 34.
    Quach K, Grover SA, Kenigsberg S, Librach CL. A combination of single nucleotide polymorphisms in the 3′untranslated region of HLA-G is associated with preeclampsia. Hum Immunol. 2014;75(12):1163–70. Scholar
  35. 35.
    Rousseau P, Discorde ML, Mouillot G, Marcou C, Carsella ED, Moreau P. The 14 bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol 2003;64(11):1005–10. Scholar
  36. 36.
    O’Brien M, McCarthy T, Jenkins D, Paul P, Dausset J, Carosella ED, et al. Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease. Cell Mol Life Sci. 2001;58:1943–9. Scholar
  37. 37.
    Chen P, Gong Y, Pu Y, Wang Y, Zhou B, Song Y, et al. Association between polymorphisms in IL-27 gene and pre-eclampsia. Placenta. 2016;37:61–4. Scholar
  38. 38.
    Liu B, Li Y, Yao Y, Li H, Liang H, Xin M, et al. Polymorphisms of the IL27 gene in a Chinese Han population complicated with pre-eclampsia. Sci Rep. 2016;6:1–6.CrossRefGoogle Scholar
  39. 39.
    Zhang X, Jiang Y, Liu Y, Wang L. Association between interleukin-4 C-590T and C+33T genetic polymorphisms and risk of preeclampsia in pregnant women of Central China. Int J Clin Exp Pathol. 2017;10(3):3438–44.Google Scholar
  40. 40.
    Fraser R, Walker JJ, Ekbote UV, Martin KL, McShane P, Orsi NM. Interleukin-4 –590 (C>T), toll-like receptor-2 +2258 (G>a) and matrix metalloproteinase-9 –1562 (C>T) polymorphisms in pre-eclampsia. BJOG. 2008;115:1052–6. Scholar
  41. 41.
    Salimi S, Mohammadoo-Khorasani M, Yaghmaei M. Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia. Biomed Res Int. 2014;2014:1–5.Google Scholar
  42. 42.
    Andraweera PH, Dekker GA, Jayasekara RW, Dissanayake VHW, Roberts CT. Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women J Matern Fetal Neonatal Med. 2015;Early Online:1–5.Google Scholar
  43. 43.
    Pontillo A, Reis EC, Bricher PN, Vianna P, Diniz S, Fernandes KS, et al. NLRP1 L155H polymorphism is a risk factor for preeclampsia development. Am J Reprod Immunol. 2015;73(6):577–81. Scholar
  44. 44.
    Wang X, Liu M, Liu Z, Niu Z, Liu S. The association of CARD8 rs2043211 polymorphism with preeclampsia in the Chinese Han population. Gynecol Obstet Investig. 2015;80(3):1–6.CrossRefGoogle Scholar
  45. 45.
    Hennessy A, Pilmore HL, Simmons LA, Painter DM. A deficiency pf placental IL-10 in pre-eclmapsia. J Immunol. 1999;163:3491–5.PubMedGoogle Scholar
  46. 46.
    Serrano NC. Immunology and genetic of preeclampsia. Clin Dev Immunol. 2006;13(2–4):197–201.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Sowmya S, Ramaiah A, Sunitha T, Nallari P, Jyothy A, Venkateshwari A. Evaluation of Interleukin-10 (G-1082A) promoter polymorphism in preeclampsia. J Reprod Infertil. 2013;14(2):62–6.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Lee YH, Kim JH, Song GG. Meta-analysis of associations between interleukin-10 polymorphisms and susceptibility to pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2014;182:202–7. Scholar
  49. 49.
    Mulla MJ, Myrtolli K, Potter J, Boeras C, Kavathas PB, Sfakianaki AK, et al. Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol. 2010;65:542–8.CrossRefGoogle Scholar
  50. 50.
    Hawkins T, Roberts J, Mangos G, Davis G, Roberts L, Brown M. Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study. BJOG. 2012;119:484–92. Scholar
  51. 51.
    Matias ML, Romão M, Weel IC, Ribeiro VR, Nunes PR, Borges VT, et al. Endogenous and uric acid-induced activation of NLRP3 Inflammasome in pregnant women with preeclampsia. PLoS One. 2015;10(6):1–16.CrossRefGoogle Scholar
  52. 52.
    Calleja-Agius J, Muttukrishna S, Jauniaux E. The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome. Int J Interferon Cytokine Mediat Res. 2012;4:1–15.CrossRefGoogle Scholar
  53. 53.
    Moreli JB, Ruocco AM, Vernini JM, Rudge MVC, Calderon MP. Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest in clinical obstetrics. ISRN Obstet Gynecol. 2012;2012:1–5. Scholar
  54. 54.
    Hayashi M, Ueda Y, Yamaguchi T, Sohma R, Shibazaki M, Ohkura T, et al. Tumor necrosis factor-α in the placenta is not elevated in pre-eclamptic patients despite its elevation in peripheral blood. Am J Reprod Immunol. 2005;53(3):113–9. Scholar
  55. 55.
    Heiskanen J, Romppanen E, Hiltunen M, Iivonen S, Mannermaa A, Punnonen K, et al. Polymorphism in the tumor necrosis factor-α gene in women with preeclampsia. J Assist Reprod Genet. 2002;19(5):220–3. Scholar
  56. 56.
    Tan CY, Chong YS, Loganath A, Chan YH, Ravichandran J, Lee CG, et al. Possible gene-gene interaction of KIR2DL4 with its cognate ligand HLA-G in modulating risk for preeclampsia. Reprod Sci. 2009;16(12):1135–43. Scholar
  57. 57.
    Emmery J, Christiansen OB, Nilsson LL, Dahl M, Skoobo P, Moller AM, et al. OP 55 associations between fetal HLA-G genotype and birth and placenta weight in pregnancies complicated by preeclampsia and in uncomplicated pregnancies possible implications for HLA diversity. Pregnancy Hypertension. 2017;9:34–5. Scholar
  58. 58.
    Yie S, Li L, Li Y, Librach C. HLA-G protein concentrations in maternal serum and placental tissue are decreased in preeclampsia. AJOG. 2004;191(2):525–9.CrossRefGoogle Scholar
  59. 59.
    Vianna P, Mondadori AG, Bauer ME, Dornfeld D, Chies JAB. HLA-G and CD8+ regulatory T cells in the inflammatory environment of pre-eclampsia. Reproduction. 2016;152:741–51. Scholar
  60. 60.
    Mondo C, Peleri P, Mazzocco MI, Lattuada D, Zolin A, Plebani M, et al. Maternal and fetal HLA-G 14 bp gene polymorphism in pregnancy-induced hypertension, preeclampsia, intrauterine growth restricted and normal pregnancies. J Matern Fetal Neonatal Med. 2015;29(9):1509–14.CrossRefGoogle Scholar
  61. 61.
    Humphrey KE, Harrison GA, Cooper DW, Wilton AN, Brennecke SP, Trudinger BJ. HLA-G deletion polymorphism and pre-eclampsia/eclampsia. BJOG. 1995;102(9):707–10. Scholar
  62. 62.
    Dekker GA, Robillard PY. Preeclampsia: a couple’s disease with maternal and fetal manifestations. Curr Pharm Des. 2004;10:1–13.Google Scholar
  63. 63.
    Young BC, Levine RJ, Karumanchi SA. Pathogenesis of preeclampsia. Annu Rev Pathol Mech Dis. 2010;5:173–92. Scholar
  64. 64.
    Mellembakken JR, Aukrust P, Hestdal K, Ueland T, Abyholm T, Videm V. Chemokines and leukocyte activation in the fetal circulation during preeclampsia. Hypertension. 2001;38:394–8. Scholar
  65. 65.
    Liu X, Dai L, Zhou R. Association between preeclampsia and the CXC chemokine family (review). Exp Ther Med. 2015;9:1572–6. Scholar
  66. 66.
    Huber A, Grimm C, Jirecek S, Zeillinger R, Husslein P, Hefler L. Polymorphisms within the Interleukin-1 gene family and unexplained late intrauterine fetal death: a multi-center study. Am J Reprod Immunol. 2005;53:132–5. Scholar
  67. 67.
    Novakovic B, Sibson M, Ng HK, Manuelpillai U, Rakyan V, Down T, et al. 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. 2009;284:14838–48. Scholar
  68. 68.
    Bakacak M, Serin S, Ercan O, Köstü B, Avci F, Kılınç M, et al. Comparison of vitamin D levels in cases with preeclampsia, eclampsia and healthy pregnant women. Int J Clin Exp Med. 2015;8(9):16280–6.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Nassar K, Rachidi W, Janani S, Mkinsi O. Vitamin D and pre-eclampsia. Gynecol Obstet. 2016;6(6):1–4.CrossRefGoogle Scholar
  70. 70.
    Liu NQ, Kaplan AT, Lagishetty V, Onyang YB, Onyang Y, Simmons CF, et al. Vitamin D and the regulation of placental inflammation. J Immunol. 2011;186:1–9.CrossRefGoogle Scholar
  71. 71.
    Ma R, Gu Y, Zhao S, Jingxia S, Groome LJ, Wang Y. Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. Am J Physiol Endocrinol Metab. 2012;303:1–8.CrossRefGoogle Scholar
  72. 72.
    Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA. Interferon gamma in successful pregnancies. Biol Reprod. 2009;80:848–59. Scholar
  73. 73.
    Taylor BD, Ness RB, Klebanoff MA, Zoh R, Bass D, Hougaard DM, et al. First and second trimester immune biomarkers in preeclamptic and normotensive women. Pregnancy Hypertens. 2016;6(4):388–93. Scholar
  74. 74.
    de Lima TH, Sass N, Mattar R, Moron AF, Torloni MR, Franchin CS, et al. Cytokine gene polymorphisms in preeclampsia and eclampsia. Hypertens Res. 2009;32:565–9. Scholar
  75. 75.
    Venkatesha S, Toporsian M, Lam C, Hanani J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6):642–9. Scholar
  76. 76.
    Govender N, Naicker T, Rajakumar A, Moodley J. Soluble fms-like tyrosine kinase-1 and soluble endoglin in HIV-associated pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2013;170:100–5. Scholar
  77. 77.
    Ramma W, Buhimschi IA, Zhao G, Dulay AT, Nayeri UA, Buhimschi CS, et al. The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia. Angiogenesis. 2012;15:333–40. Scholar
  78. 78.
    Powers RW, Jeyabalan A, Clifton RG, Doraten PV, Hauth JC, Klebanoff MA, et al. Soluble fms-like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One. 2010;5(10):1–12.CrossRefGoogle Scholar
  79. 79.
    Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR, Granger JP. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2008;294:H541–50. Scholar
  80. 80.
    Maynard SE, Venkatesha S, Thandani R, Karumanchi SA. Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia. Pediatr Res. 2005;57:1R–7R. Scholar
  81. 81.
    Cerdeira AS, Karumanchi SA. Angiogenic factors in preeclampsia and related disorders. Perspect Med. 2012;2:1–18.Google Scholar
  82. 82.
    Singh A, Sharma D, Raghunandan C, Bhattacharjee J. Role of inflammatory cytokines and eNOS gene polymorphism in pathophysiology of pre-eclampsia. Am J Reprod Immunol. 2010;63:244–51. Scholar
  83. 83.
    Mello G, Parretti E, Genrini F, Sticchi E, Macacci F, Scarselli G, et al. Maternal-fetal flow, negative events, and preeclampsia role of ACE I/D polymorphism. Hypertension. 2003;41:932–7. Scholar
  84. 84.
    Anton L, Brosnihan KB. Systemic and uteroplacental renin–angiotensin system in normal and pre-eclamptic pregnancies. Ther Adv Cardiovasc Dis. 2008;2(5):349–62. Scholar
  85. 85.
    Roberts CB, Rom L, Moodely J, Pegararo RJ. Hypertension-related gene polymorphisms in pre-eclampsia, eclampsia and gestational hypertension in Black South African women. J Hypertens. 2004;22(5):945–8. Scholar
  86. 86.
    Li H, Ma Y, Fu Q, Wang L. Angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor (AT1R) gene polymorphism and its association with preeclampsia in Chinese women. Hypertens Pregnancy. 2009;26(3):293–301.CrossRefGoogle Scholar
  87. 87.
    Belo L, Caslake M, Gaffney D, Santos-Silva A, Pereira-Leite L, Quintanilha A, et al. Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis. 2002;162:425–32. Scholar
  88. 88.
    Belo L, Gaffney D, Caslake M, Santos-Silva A, Pereira-Leite L, Quintanilha A, et al. Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies. Eur J Obstet Gynecol Reprod Biol. 2004;112:9–15. Scholar
  89. 89.
    Chikosi AB, Moodley J, Moodley J, Pegoraro RJ, Lanning PA, Rom L. Apolipoprotein e polymorphism in South African Zulu women with preeclampsia. Hypertens Pregnancy. 2009;19(3):309–14.CrossRefGoogle Scholar
  90. 90.
    Zhao L, Triche EW, Walsh KM, Bracken MB, Saftas AF, Hoh J, et al. Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients. BMC Pregnancy Childbirth. 2012;12(61):1–10.Google Scholar
  91. 91.
    Zhao L, Bracken MB, Dewan AT. Genome-wide association study of preeclampsia detects novel maternal single nucleotide polymorphisms and copy-number variants in subsets of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort. Ann Hum Genet. 2013;77(4):277–87. Scholar
  92. 92.
    Laivuori H, Lehermo P, Ollikainen V, Widen E, Haiva-Mallinen L, Sundstrom H, et al. Susceptibility loci for preeclampsia on chromosomes 2p25 and 9p13 in Finnish families. Am J Hum Genet. 2003;72:168–77. Scholar
  93. 93.
    Arngrímsson R, Sigurardóttir S, Frigge ML, Bjarnadóttir RI, Jónsson T, Stefánsson H, et al. A genome-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13. Hum Mol Genet. 1999;8:1799–805. Scholar
  94. 94.
    Johnson MP, Brennecke SP, East CE, Goring HHH, Kent JW Jr, Dyer TD, et al. Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, Beta B Gene. PloS One. 2012;7(3):1–12.Google Scholar
  95. 95.
    Moses EK, Lade JA, Guo G, Wilton AN, Grehan M, Freed K, et al. A genome scan in Australian and New Zealand families confirms the presence of a maternal susceptibility locus for pre-eclampsia on chromosome 2. Am J Hum Genet. 2000;67:1581–5. Scholar
  96. 96.
    Johnson MP, Roten LT, Dyer TD, East CE, Forsmo S, Blangero J, et al. The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. Hum Genet. 2009;126(5):655–66. Scholar
  97. 97.
    Williams PJ, Pipkin FB. The genetics of pre-eclampsia and other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25:405–17. Scholar
  98. 98.
    Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001;357(9249):53–6. Scholar
  99. 99.
    Wilton AN, Cooper DW, Marshall P, Brennecke SP, Bishop SM. Absence of close linkage between maternal genes for susceptibility to pre-eclampsia/eclampsia and HLA DRβ. Lancet. 1990;336(8716):653–7. Scholar
  100. 100.
    Hayward C, Livingstone J, Holloway S, Liston WA, Brock DJH. An exclusion map for pre-eclampsia: assuming autosomal recessive inheritance. Am J Hum Genet. 1992;50:749–57.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Rabaglino MB, Post Uiterweer ED, Jeyabalan A, Hogge WA, Gonrad KP. Bioinformatics approach reveals evidence for impaired endometrial maturation before and during early pregnancy in women who developed preeclampsia. Hypertension. 2015;65:1–9.CrossRefGoogle Scholar
  102. 102.
    Tejera E, Bernardes J, Rebelo I. Preeclampsia: a bioinformatics approach through protein-protein interaction networks analysis. BMC Syst Biol. 2012;6(9):1–9.Google Scholar
  103. 103.
    Tejera E, Bernardes J, Rebelo I. Co-expression network analysis and genetic algorithms for gene prioritization in preeclampsia. BMC Med Genet. 2013;6(51):1–17.Google Scholar
  104. 104.
    Song J, Li Y, An RF. Identification of early-onset preeclampsia-related genes and MicroRNAs by bioinformatics approaches. Reprod Sci. 2015;22(8):954–63. Scholar
  105. 105.
    Ching T, Ha J, Song M-A, Tiirkainen M, Molnar J, Berry MJ, et al. Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia. Clin Epigenetics. 2015;7(21):1–15.Google Scholar
  106. 106.
    Maharaj NR, Ramkaran P, Pillay S, Chuturgoon AA. MicroRNA-146a rs2910164 is associated with severe preeclampsia in Black South African women on HAART. BMC Genet. 2017;18(5):1–9.Google Scholar
  107. 107.
    Maharaj NR, Phulukdaree A, Nagiah S, Ramkaram P, Tiloke C, Chuturgoon AA. Pro-inflammatory cytokine levels in HIV infected and uninfected pregnant women with and without preeclampsia. PLoS One. 2017;12(1):1–9.CrossRefGoogle Scholar
  108. 108.
    Chen D-b, Wang W. Human placental microRNAs and preeclampsia. Biol Reprod. 2013;88(5):1–11.CrossRefGoogle Scholar
  109. 109.
    Aung M, Konoshita T, Moodley J, Gathiram P. Association of gene polymorphisms of aldosterone synthase and angiotensin converting enzyme in pre-eclamptic South African Black women. Pregnancy Hypertens. 2018;11:38–43. Scholar
  110. 110.
    Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329:841–5. Scholar
  111. 111.
    •• Kasembeli AN, Duarte R, Ramsay M, Mosiane P, Dickens C, Dix-Peek T, et al. APOL-1 risk variants are strongly associated with HIV-associated nephropathy in Black South Africans. J Am Soc Nephrol. 2015;26:2882–90. This article reports the strong association between Apol-1 gene polymorphisms and kidney disease. A noteworthy occurrence that should be investigated in pre-eclampsia.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Norwitz ER, Repke JT. Acute complications of preeclampsia. Clin Obstet Gynecol. 2002;45(2):308–29. Scholar
  113. 113.
    Davis R, Simpson C, Tylavsky F, Reidy K, HJorten R, Rosenberg A, et al. Infant but not maternal APOL1 variant genotypes are associated with increased risk for preeclampsia in African Americans. Pregnancy Hypertens. 2017;9:55.CrossRefGoogle Scholar
  114. 114.
    Brew O, Sullivan MHF, Woodman A. Comparison of the normal and pre-eclamptic placental gene expression: a systematic review with meta-analysis. PLoS One. 2016;11(8):1–20.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Semone Thakoordeen
    • 1
    Email author
  • Jagidesa Moodley
    • 1
  • Thajasvarie Naicker
    • 2
  1. 1.Women’s Health and HIV Research Group, Department of Obstetrics and GynaecologyUniversity of KwaZulu-NatalKwaZulu-NatalSouth Africa
  2. 2.Optics and Imaging CentreUniversity of KwaZulu-NatalKwaZulu-NatalSouth Africa

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