FACTORS OF HEREDITARY PREDISPOSITION FOR PREECLAMPSIA: GENERALIZATION OF DATA OF META-ANALYSES

DOI: https://doi.org/None

E.A. Trifonova (1,3), T.V. Gabidulina (2), I.U. Bukharina (2), V.A. Stepanov (1,3) 1 -Research Institute of Medical Genetics, Naberezhnaya Ushaiki, 10, Tomsk, 634050, Russian Federation; 2 -Research Institute of Obstetrics and Gynecology, Sergeya Lazo Str., 5, Tomsk, 634063, Russian Federation; 3 -Tomsk State University, Lenina Avenue, 36, Tomsk, 634050, Russian Federation

Preeclampsia is the pregnancy complication characterized by the presence of arterial hypertension and proteinuria. Preeclampsia is the leading cause of maternal and perinatal morbidity and mortality. To date, there are more than 40 advanced theories of etiopathogenesis of preeclampsia, including the theory of genetic determinancy. However, the proposed hypotheses neither fully explains mechanisms of the disease nor determines unambiguously factors that predispose to its development. The role of genetic factors in susceptibility to preeclampsia is discussed in the review. There was performed the generalization of results of meta-analyzes of studies of the association of allelic variants of candidate genes for this pathology, and the functional significance of an array of associated polymorphic markers of genes of renin-angiotensin-aldosterone system, folate metabolism, clotting and fibrinolysis factors was characterized. There is shown the importance of the considering of the ethnic affiliation of individuals in the study of genetic factors in the development of preeclampsia. The possible factors contributing to the inconsistency of results of meta-analyzes, obtained by different researchers, are discussed.
Keywords: 
preeclampsia, polymorphic variant, gene, genetic predisposition, meta-analysis
Список литературы: 
  1. Hodzhaeva Z.S., Kogan E.A., Safonova A.D., Akat`eva A.S., Muminova K.T., Fayzullin A.L. Placentarnoe lozhe i pree`klampsiya. Akusherstvo i ginekologiya. 2013; 12: 10–5.[Hodzhaeva Z.S., Kogan E.A., Safonova A.D., Akat’eva A.S., Muminova K.T., Fajzullin A.L. Placentarnoe lozhe i prejeklampsija. Akusherstvo i ginekologija. 2013; 12: 10–5 (in Russian)]
  2. Boyd H., Tahir H., Wohlfahrt J., Melbye M. Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia. Am. J. Epidemiol. 2013; 12: 1611–9.
  3. Aylamazyan E`.K., Mozgovaya E.V. Gestoz: teoriya i praktika. M., 2008. [Ajlamazjan Je.K., Mozgovaja E.V. Gestoz: teorija i praktika. M., 2008 (in Russian)]
  4. Valenzuela F.J., Pérez-Sepúlveda A., Torres M.J., Correa P., Repetto G.M., Illanes S.E. Pathogenesis of Preeclampsia: The Genetic Component. J. Pregnancy. 2012; 2012: e632732.
  5. Lardoeyt R., Vargas G., Lumpuy J., Garcia R., Torres Y. Contribution of genome–environment interaction to pre-eclampsia in a Havana Maternity Hospital. MEDICC Review. 2013; 15 (3): 22–9.
  6. Lokki A.I., Klemetti M.M., Heino S. Association of the rs1424954 polymorphism of the ACVR2A gene with the risk of pre-eclampsia is not replicated in a Finnish study population. BMC Res Notes. 2011; 4: 545.
  7. Ros H.S., Lichtenstein P., Lipworth L., Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Genet. 2000; 91 (4): 256–60.
  8. Nilsson E., Ros H.S., Cnattingius S., Lichtenstein P. The importance of genetic and environmental effects for pre-eclampsia and gestational hypertension: a family study. BJOG. 2004; 111 (3): 200–6.
  9. Arngrimsson R., Bjornsson S., Geirsson R., Bjornsson H., Walker J.J., Snaedal G. Genetic and familial predisposition to eclampsia and pre-eclampsia in a defined population. Br J Obstet Gynaecol. 1990; 97: 762–9.
  10. Berends A.L., Steegers E.A., Isaacs A., Aulchenko Y.S., Liu F., de Groot C.J. Oostra B.A., van Duijn C.M. Familial aggregation of preeclampsia and intrauterine growth restriction in a genetically isolated population in The Netherlands. Eur. J. Hum. Genet. 2008; 16 (12): 1437–42.
  11. Lie R., Rasmussen S., Brunborg H. Fetal and matemal contributions to risk of Preeclampsia: population based study. BML. 1998; 316: 1343–7.
  12. Dekker G., Robillard P.Y., Roberts C. The etiology of preeclampsia: the role of the father. J Reprod Immunol. 2011; 89: 126–32.
  13. Mütze S., Rudnik–Schöneborn S., Zerres K., Rath W. Genes and the preeclampsia syndrome. J. Perinat. Med. 2008; 36 (1): 38–58.
  14. Wang X.M., Wu H.Y., Qiu X.J. Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and risk of preeclampsia: an updated meta-analysis based on 51 studies. Arch Med Res. 2013; 44 (3): 159–68.
  15. Xia X.P., Chang W.W., Cao Y.X. Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to pre-eclampsia. Hypertens Res. 2012; 35 (12): 1129–34.
  16. Lin J., August P. Genetic thrombophilias and preeclampsia: a meta-analysis. J. Obstet. Gynecol. 2005; 105 (1): 182–92.
  17. Buurma A.J., Turner R.J., Drissen J.H., Mooyaart A.L., Schoones J.W., Bruijn J.A., Bloemenkamp K.W., Dekkers O.M., Baelde H.J. Genetic variants in pre-eclampsia: a meta-analysis. Hum Reprod Update. 2013. 19 (3): 289–303.
  18. Kosmas I.P., Tatsioni A., Ioannidis J.P. Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J. Hypertens. 2004; 22 (9): 1655–62.
  19. Song C., Xie S., Wang J. Association of angiotensinogen gene polymorphisms and angiogenic factors with preeclampsia in Chinese women. Gynecol. Obstet. Invest. 2013; 76 (1): 64–8.
  20. Morgan J.A., Bombell S., McGuire W. Association of plasminogen activator inhibitor-type 1 (-675 4G/5G) polymorphism with pre-eclampsia: systematic review. PLoS One. 2013; 8 (2): e364.
  21. Zhao L., Bracken M.B., Dewan A.T., Chen S. Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and preeclampsia: a systematic review and meta-analysis. Mol. Hum. Reprod. 2013; 19 (3): 136–43.
  22. Wiwanitkit V. Correlation between plasminogen activator inhibitor-1 4G/5G polymorphism and pre-eclampsia: an appraisal. Arch. Gynecol. Obstet. 2006; 273 (6): 322–4.
  23. Qi H.P., Fraser W.D., Luo Z.C., Wei S.Q. Endothelial nitric oxide synthase gene polymorphisms and risk of preeclampsia. Am J Perinatol. 2013; 30 (10): 795–804.
  24. Chen H., Zhao G., Sun M., Wang H., Liu J., Gao W., Meng T. Endothelial nitric oxide synthase gene polymorphisms (G894T, 4b/a and T-786C) and preeclampsia: meta-analysis of 18 case-control studies. DNA Cell Biol. 2012; 31 (6): 1136–45.
  25. Dai B., Liu T., Zhang B., Zhang X., Wang Z. The polymorphism for endothelial nitric oxide synthase gene, the level of nitric oxide and the risk for pre-eclampsia: a meta-analysis. Gene. 2013; 519 (1): 187–93.
  26. Shaik A.P., Sultana A., Bammidi V.K., Sampathirao K., Jamil K. A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women. J Obstet Gynaecol. 2011; 31 (7): 603–7.
  27. Medica I., Kastrin A., Peterlin B. Genetic polymorphisms in vasoactive genes and preeclampsia: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2007; 131 (2): 115–26.
  28. Yu C.K., Casas J.P., Savvidou M.D., Hingorani A.D. Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and development of pre-eclampsia: a case-control study and a meta-analysis. BMC Pregnancy Childbirth. 2006; 16: 6–7.
  29. Zhong W.G., Wang Y., Zhu H., Zhao X. Meta analysis of angiotensin-converting enzyme I/D polymorphism as a risk factor for preeclampsia in Chinese women. Genet Mol Res. 2012; 11 (3): 2268–76.
  30. Zhu M., Zhang J., Nie S., Yan W. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis. J. Assist Reprod Genet. 2012; 29 (9): 921–32.
  31. Chen Z., Xu F., Wei Y., Liu F., Qi H. Angiotensin converting enzyme insertion/deletion polymorphism and risk of pregnancy hypertensive disorders: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2012; 13: 184–95.
  32. Serrano N.C., Diaz L.A., Páez M.C., Mesa C.M., Cifuentes R., Monterrosa A., Hingorani A.D., Casas J.P. Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias. PLoS Med. 2006; 3 (12): e520.
  33. Ni S., Zhang Y., Deng Y., Gong Y., Huang J., Bai Y., Zhou R. AGT M235T polymorphism contributes to risk of preeclampsia: evidence from a meta-analysis. J. Renin Angiotensin Aldosterone Syst. 2012; 3 (3): 379–86.
  34. Lin R., Lei Y., Yuan Z., Ju H., Li D. Angiotensinogen gene M235T and T174M polymorphisms and susceptibility of pre-eclampsia: a meta-analysis. Ann Hum Genet. 2012; 76 (5): 377–86.
  35. Zafarmand M. H., Franx A., Sabour S., Grobbee D.E., Bots M.L. The M235T variant of the angiotensinogen gene is related to development of self-reported hypertension during pregnancy: the Prospect-EPIC cohort study. J Hypertens Res. 2008; 31: 1299–305.
  36. Zhao L., Dewan A.T., Bracken M.B. Association of maternal AGTR1 polymorphisms and preeclampsia: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2012; 25 (12): 2676–80.
  37. Rodger M.A., Betancourt M.T., Clark P., Lindqvist P.G., Dizon-Townson D., Said J., Seligsohn U., Carrier M., Salomon O., Greer I.A. The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies. PLOS Medicine. 2010; 7: 1–12.
  38. Dudding T., Heron J., Thakkinstian A., Nurk E., Golding J., Pembrey M. Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis. J. Thromb Haemost. 2008; 6 (11): 1869–75.
  39. Kosmas I.P., Tatsioni A., Ioannidis J.P. Association of Leiden mutation in factor V gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J. Hypertens. 2003; 21: 1221–8.
  40. Xie C., Yao M.Z., Liu J.B., Xiong L.K. A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia. Cytokine. 2011; 56 (3): 550–9.
  41. Bombell S., McGuire W. Tumour necrosis factor (-308A) polymorphism in pre-eclampsia: meta-analysis of 16 case-control studies. Aust. N. Z. J. Obstet Gynaecol. 2008; 48: 547–51.
  42. Molvarec A., Jermendy A., Nagy B. Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction. Clin. Chim. Acta. 2008; 392 (1): 52–7.
  43. Bailey L.B., Gregory J.F. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J. Nutr. 1999; 129 (5): 919–22.
  44. Murphy M.M. Fernandez-Ballart J.D. Homocysteine in pregnancy. Adv. Clin. Chem. 2011; 53: 105–37.
  45. Eriksson P., Kallin B., vant’t Hooft F.M. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA. 1995; 92 (6): 1851–15.
  46. Margaglione M., Grandone E., Vecchione G. Plasminogen activator inhibitor-1 (PAI-1) antigen plasma levels in subjects attending a metabolic ward: relation to polymorphisms of PAI-1 and angiontensin converting enzyme (ACE) genes. Arterioscler Thromb Vasc Biol. 1997; 10: 2082–7.
  47. Ramón L.A., Gilabert–Estellés J., Cosin R., Gilabert J., España F., Castelló R. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and endometriosis. Influence of PAI-1 polymorphism on PAI-1 antigen and mRNA expression. Thromb Res. 2008; 122 (6): 854–60.
  48. Zaynulina M.S., Bikmullina D.R., Kornyushina E.A. Trombofiliya: e`tiologicheskiy faktor ili patogeneticheskiy aspekt oslozhnennogo techeniya beremennosti? Zhurnal akusherstva i zhenskih bolezney. 2010; LIX (1): 18–30.[Zajnulina M.S., Bikmullina D.R., Kornjushina E.A. Trombofilija: jetiologicheskij faktor ili patogeneticheskij aspekt oslozhnennogo techenija beremennosti? Zhurnal akusherstva i zhenskih boleznej. 2010; LIX (1): 18–30 (in Russian)]
  49. Ohtyrskaya T.A., Yavorovskaya K.A., Fayzullina N.M., Demura N.M., Fayzullina L.S. Ezhova. Rol` PAI-1 v povtornyh neudachah VRT. Problemy reprodukcii. 2011; 4: 45–9.[Ohtyrskaja T.A., Javorovskaja K.A., Fajzullina N.M., Demura N.M., Fajzullina L.S. Ezhova. Rol’ PAI-1 v povtornyh neudachah VRT. Problemy reprodukcii. 2011; 4: 45–9 (in Russian)]
  50. Coolman M., Timmermans S., de Groot C.J. Angiogenic and fibrinolytic factors in blood during the first half of pregnancy and adverse pregnancy outcomes. Obstet Gynecol. 2012; 119 (6): 1190–200.
  51. Orange S.J., Painter D., Horvath J., Yu B., Trent R., Hennessy A. Placental endothelial nitric oxide synthase localization and expression in normal human pregnancy and pre-eclampsia. Clin Exp Pharmacol Physiol. 2003; 30 (5): 376–81.
  52. Wang J., Dudley D., Wang X.L. Haplotype-specific effects on endothelial NO synthase promoter efficiency modifiabe by cigarette smocing. Arterioscler Thromb Vasc Biol. 2002; 22: 1–4.
  53. Su M.T., Lin S.H., Chen Y.C. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum. Reprod. Update. 2011; 1: 1–10.
  54. Casas J.P., Cavalleri G.L., Bautista L.E., Smeeth L., Humphries S.E., Hingorani A.D. Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. Am. J. Epidemiol. 2006; 15: 921–35.
  55. Ortlepp J.R., Metrikat J., Mevissen V., Schmitz F., Albrecht M., Maya-Pelzer P., Hanrath P., Zerres K., Hoffmann R. Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population. J. Hum. Hypertens. 2003; 17 (8): 555–9.
  56. Konoshita T. Genomic Disease Outcome Consortium (G-DOC) Study Investigators. Do genetic variants of the Renin-Angiotensin system predict blood pressure response to Renin-Angiotensin system-blocking drugs? Curr Hypertens Rep. 2011;13 (5): 356–61.
  57. Yang J., Shang J., Zhang S., Li H., Liu H. The role of the renin-angiotensin-aldosterone system in preeclampsia: genetic polymorphisms and microRNA. J. Mol. Endocrinol. 2013; 50 (2): 53–66.
  58. Bicadze V.O., Makacariya A.D., Hizroeva D.H., Makacariya N.A., Yashenina E.V. Trombofiliya kak vazhneyshee zveno patogeneza oslozhneniy beremennosti. Prakticheskaya medicina. 2012; 5 (60): 22–9.[Bicadze V.O., Makacarija A.D., Hizroeva D.H., Makacarija N.A., Jashenina E.V. Trombofilija kak vazhnejshee zveno patogeneza oslozhnenij beremennosti. Prakticheskaja medicina. 2012; 5 (60): 22–9 (in Russian)]
  59. Bradley L.A., Palomaki G.E., Bienstock J., Varga E., Scott J.A. Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review. Genet Med. 2012; 14 (1): 39–50.
  60. Dissanayake V.H., Weerasekera L.Y., Gammulla C.G., Jayasekara R.W. Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services. Exp. Mol. Pathol. 2009; 87 (2): 159–62.
  61. Kupferminc M. Thrombophilia and pregnancy. Curr. Pharm. Des. 2005; 11 (6): 735–48.
  62. Halford-Knyazeva I.P., Radzinskiy V.E., Samohodskaya L.M., Yarovaya E. Geneticheskie markery prognozirovaniya pree`klampsii. Doktor.Ru. 2013; 7 (85): 58–66.[Halford-Knjazeva I.P., Radzinskij V.E., Samohodskaja L.M., Jarovaja E. Geneticheskie markery prognozirovanija prejeklampsii. Doktor.Ru. 2013; 7 (85): 58–66 (in Russian)]
  63. Rad`kov O.V., Zavarin V.V., Kalinkin M.N. Analiz associacii polimorfizma vazoaktivnyh genov s pree`klampsiey. Byulleten` Vostochno-Sibirskogo nauchnogo centra SO RAMN. 2011; 5: 109–12.[Rad’kov O.V., Zavarin V.V., Kalinkin M.N. Analiz associacii polimorfizma vazoaktivnyh genov s prejeklampsiej. Bjulleten’ Vostochno-Sibirskogo nauchnogo centra SO RAMN. 2011; 5: 109–12 (in Russian)]
  64. Pavlova K.K., Trifonova E.A., Gabidulina T.V. Gotovceva L.V., Nogovicyna A.N., Maksimova N.R., Filippova R.D., Stepanov V.A. Molekulyarno-geneticheskoe izuchenie gestoza v yakutskoy populyacii. Medicinskaya genetika. 2011; 10 (12): 28–34.[Pavlova K.K., Trifonova E.A., Gabidulina T.V. Gotovceva L.V., Nogovicyna A.N., Maksimova N.R., Filippova R.D., Stepanov V.A.. Molekuljarno-geneticheskoe izuchenie gestoza v jakutskoj populjacii. Medicinskaja genetika. 2011; 10 (12): 28–34 (in Russian)]
  65. Trifonova E.A., Gabidulina T.V., Agarkova T.A., Serebrova V.N., Butko Yu.K., Vorozhishheva A.Yu., Yur`ev S.Yu., Devyat`yarova L.A., Minaycheva L.I., Stepanov V.A. Analiz roli nasledstvennoy trombofilii v razvitii oslozhnennogo techeniya beremennosti. Fundamental`nye issledovaniya. 2012; 10–2: 337–44.[Trifonova E.A., Gabidulina T.V., Agarkova T.A., Serebrova V.N., Butko Ju.K., Vorozhishheva A.Ju., Jur’ev S.Ju., Devjat’jarova L.A., Minajcheva L.I., Stepanov V.A. Analiz roli nasledstvennoj trombofilii v razvitii oslozhnennogo techenija beremennosti. Fundamental’nye issledovanija. 2012; 10–2: 337–44 (in Russian)]