Mini-symposium: The pathogenesis of pre-eclampsia| Volume 9, ISSUE 4, P178-182, December 1999

Genetics of pre-eclampsia: ideas at the turn of the millennium

      This paper is only available as a PDF. To read, Please Download here.


      The causes of pre-eclampsia (PE) remain enigmatic, but there is a genetic component. The diagnosis probably covers several conditions but it is, in any case, a multifactorial disease; there will not be a single ‘PE gene’, but interactions between several genes, and between them and the environment, may predispose to it. Several polymorphisms of genes involved in the clotting cascade may predispose to PE, but are not pre-requisites. Among these are the polymorphisms Factor V Leiden and C677T methylenetetrahydrofolate reductase (MTHFR); both have functional consequences. In some, but not all, populations, there is an increased frequency of the M235T variant of the angiotensinogen gene in women with PE. However, this polymorphism also has an increased incidence in essential hypertension and coronary heart disease. There is significantly distorted maternal–fetal transmission of a dinucleotide repeat polymorphism of the angiotensinogen gene in PE, associated with low plasma-angiotensinogen concentrations, and of a similar polymorphism in the Type 1 angiotensin receptor. There is no evidence at present for a genetic involvement of the HLA system. The complex nature of PE means that large-scale studies of carefully-phenotyped women will be needed to unravel the genetic contribution to its pathogenesis. Such a study is just beginning in the UK (the GOPEC study).
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Obstetrics, Gynaecology and Reproductive Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect



        • Arngrimsson R.
        • Björnsson S.
        • Geirsson R.T.
        • Björnsson 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: 762-769
        • Graves J.A.M.
        Genomic imprinting, development and disease – is pre-eclampsia caused by a maternally-imprinted gene?.
        Reprod Fertil Dev. 1998; 10: 23-29
        • Jonsdottir L.S.
        • Arnsgrimsson R.
        • Geirsson R.T.
        • Sigvaldson H.
        • Sigfusson N.
        Death rates from ischaemic heart disease in women with a history of hypertension in pregnancy.
        Acta Obstet Gynecol Scand. 1995; 74: 772-776
        • Chesley L.C.
        • Cooper D.W.
        Genetics of hypertension in pregnancy: possible single-gene control of pre-eclampsia and eclampsia in the descendants of eclamptic women.
        Br J Obstet Gynaecol. 1986; 93: 898-908
        • Lie R.T.
        • Rasmussen S.
        • Brunborg H.
        • Gjessing K.
        • Lie-Nielsen Irgens L.M.
        Fetal and maternal contributions to risk of pre-eclampsia: population-based study.
        BMJ. 1998; 316: 1343-1347
        • Arngrimsson R.
        • Hayward C.
        • Nadaud S.
        Evidence for a familial pregnancy-induced hypertension locus in the eNOS gene region.
        Am J Hum Genet. 1997; 61: 354-362
        • Kilpatrick D.C.
        • Gibson F.
        • Livingstone J.
        • Liston W.A.
        Pre-eclampsia is associated with HLA-DR4 sharing between mother and fetus.
        Tissue Antigens. 1990; 35: 178-181
        • Wilton An
        • Cooper D.W.
        • Brennecke S.P.
        • Bishop S.M.
        • Marshall P.
        Absence of close linkage between maternal genes for susceptibility to pre-eclampsia/eclampsia and HLA DRβ.
        Lancet. 1990; 336: 653-657
        • Humphrey K.E.
        • Harrison G.A.
        • Cooper D.W.
        • Wilton A.N.
        • Brennecke S.P.
        • Trudinger B.J.
        HLA-G deletion polymorphism and pre-eclampsia-eclampsia.
        Br J Obstet Gynaecol. 1995; 102: 707-710
        • Chen G.
        • Wilson R.
        • Wang S.H.
        • Zheng H.Z.
        • Walker J.J.
        • McKillop J.H.
        Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia.
        Clin Exp Immunol. 1996; 104: 154-159
        • Dizon-Townson D.S.
        • Major H.
        • Ward K.
        A promoter mutation in the tumor necrosis factor alpha gene is not associated with pre-eclampsia.
        Reprod Immunol. 1998; 38: 55-61
        • Arngrimsson R.
        • Geirsson R.T.
        • Connor M.
        • Björnsson S.
        • Walker J.J.
        Renin gene restriction fragment length polymorphisms do not show linkage with pre-eclampsia and eclampsia.
        Acta Obstet Gynecol Scand. 1994; 73: 10-13
        • Powers R.W.
        • Minich L.A.
        • Lykins D.L.
        • Ness R.B.
        • Crombleholme W.R.
        • Roberts J.M.
        Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to pre-eclampsia.
        J Soc Gynecol Investig. 1999; 6: 74-79
        • Kupferminc M.J.
        • Eldor A.
        • Steinman N.
        Increased frequency of genetic thrombophilia in women with complications of pregnancy.
        N Engl J Med. 1999; 340: 9-13
        • Lindoff C.
        • Ingemarsson I.
        • Matinsson G.
        • Segelmark M.
        • Thysell H.
        • Astedt B.
        Pre-eclampsia is associated with a reduced response to activated protein C.
        Am J Obstet Gynecol. 1997; 176: 457-460
        • Ward K.
        • Hata A.
        • Jeunemaitre X.
        A molecular variant of angiotensinogen associated with pre-eclampsia.
        Nature Genet. 1993; 4: 59-61
        • Kobashi G.
        A case-control study of pregnancy-induced hypertension with a genetic predisposition: association of a molecular variant of angiotensinogen in Japanese women.
        Hokkaido J med Sci. 1995; 70: 649-657
        • Caulfield M.
        • Lavender P.
        • Newell-Price J.
        • Kamdar S.
        • Farrell M.
        • Clark A.J.L.
        Angiotensinogen in human essential hypertension.
        Hypertension. 1996; 28: 1123-1125
        • Morgan L.
        • Baker P.N.
        • Broughton Pipkin F.
        • Kalsheker N.
        Pre-eclampsia and the angiotensinogen gene.
        Br J Obstet Gynecol. 1995; 102: 489-490
        • Guo G.
        • Wilton A.N.
        • Fu Y.
        • Qiu H.
        • Brennecke S.P.
        • Cooper D.W.
        Angiotensinogen gene variation in a population case-control study of pre-eclampsia/eclampsia in Australians and Chinese.
        Electrophoresis. 1997; 18: 1646-1649
        • Morgan L.
        • Crawshaw S.
        • Baker P.N.
        • Broughton Pipkin F.
        • Kalsheker N.
        Maternal and fetal angiotensinogen gene allele sharing in pre-eclampsia.
        Br J Obstet Gynecol. 1999; 106: 244-251
        • Wallukat G.
        • Homuth V.
        • Fischer T.
        Patients with pre-eclampsia develop agnoistic autoantibodies against the angiotensin AT1 receptor.
        J Clin Invest,. 1999; 103: 945-952
        • Morgan L.
        • Crawshaw S.
        • Baker P.N.
        • Edwards R.
        • Broughton Pipkin F.
        • Kalsheker N.
        Functional and genetic studies of the angiotensin II type 1 receptor in pre-eclampsia and normotensive pregnant women.
        J. Hyp. 1998; 15: 1389-1396
        • Morgan L.
        • Crawshaw S.
        • Baker P.N.
        • Brookfield J.F.
        • Broughton Pipkin F.
        • Kalsheker N.
        Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.
        J Med Genet. 1998; 35: 632-636
        • Morgan T.
        • Craven C.
        • Nelson L.
        • Lalouel J.M.
        • Ward K.
        Angiotensinogen T235 expression is elevated in decidual spiral arteries.
        J Clin Invest. 1997; 100: 1406-1415
        • Takimoto E.
        • Ishida J.
        • Sugiyama F.
        • Horiguchi H.
        • Murakami K.
        • Fukamizu A.
        Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen.
        Science. 1996; 274: 995-998