Abstract
Pregnancy–induced hypertension (PIH) is a heterogeneous disorder which complicates 5–7% of all pregnancies and remains a leading cause of maternal, fetal and neonatal morbidity and mortality. Severe preeclampsia is the most distinctive and life–threatening form; a multi–system disorder more common in first pregnancies, it is characterized by high blood pressure and proteinuria. In a series of Caucasian women with pregnancy–induced hypertension, we have observed a significant association of preeclampsia with a molecular variant of angiotensinogen, T235, found previously to be associated with essential hypertension. This finding is corroborated in a sample ascertained in Japan. Together, these observations support a new pathophysiological interpretation of preeclampsia and of its relation to some forms of essential hypertension.
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References
Chesley, L.C. & Lindheimer, M.D. Renal hemodynamics and intravascular volume in normal and hypertensive pregnancy. In Handbook of Hypertension, Vol 10: Hypertension in Pregnancy (ed. Rubin P.C.) 38–65 (Elsevier, Amsterdam, 1988).
Wallenburg, H.C.S. Hemodynamics in hypertensive pregnancy. In Handbook of Hypertension, Vol 10: Hypertension in Pregnancy (ed. Rubin P.C.) 66–101 (Elsevier, Amsterdam, 1988).
August, P. & Sealey, J.E. The renin–angiotnesin system in normal and hypertensive pregnancy and in ovarian function. In Hypertension: Pathophysiology,Diagnosis, and Management (eds Laragh, J.H. & Brenner, B.M.) 1761–1778 (Raven, New York, 1990).
Lynch, K.R. & Peach, M.J. Biochemistry and molecular biology. Hypertension 17, 263–269 (1991).
Tewksbury, D.A. Angiotensinogen: biochemistry and molecular biology. In Hypertension: Pathophysiology, Diagnosis, and Management (eds Laragh, J.H. & Brenner, B.M.) 1197–1216 (Raven, New York, 1990).
Tewksbury, D.A. & Dart, R.A. High molecular weight angiotensinogen levels in hypertensive pregnant women. Hypertension 4, 729–734 (1982).
Gant, N.F., Whalley, P.J., Everett, R.B., Worley, R.J. & MacDonald, P.C. Control of vascular reactivity in pregnancy. Am. J. kidney Dis. 9, 303–307 (1987).
Liston, W.A., & Kilpatrick, D.C. Is genetic susceptibility to pre-eclampsia conferred by homozygosity for the same signle recessive gene in mother and fetus? Br. J. Obstet. Gynecol. 98, 1079–1086 (1991).
Cooper, D.W., Hill, J.A. & Chesley, L.C. Genetic control of susceptibility to eclampsia and miscarriage. Br. J. Obstet. Gynecol. 95, 644–653 (1988).
Chesley, L.C., Annitto, J.E., & Cosgrove, R.A. The remote prognosis of eclamptic women. Am. J. Obstet. Gynecol. 124, 446–452 (1976).
Fischer, K.A., Luger, L., Spargo, B.H. & Lindheimer, M.D. Hypertension in pregnancy: clinical pathologic correlations and remote prognosis. Medicine 60, 267–272 (1981).
Gaillard, I., Clauser, E. & Corvol, P. Structure of human angiotensinogen gene. DNA 8, 87–99 (1989).
Gaillard, I., Mattei, M.G., Clauser, E. & Corvol, P. Assignment by in situ hybrization of the angiotensinogen gene to chromosome band 1q4, the same region as the human renin gene. Hum. Genet. 84, 341–343 (1990).
Jeunemaitre, X. et al. Molecular basis of human hypertension: role of angiotensiongen. Cell 71, 169–180 (1992).
Laragh, J.H. The pill, hypertension, and the toxemias of pregnancy. Am. J. Obstet. Gynecol. 109, 210–213 (1971).
Schwartz, M.L. & Brenner, W.E. Pregnancy-induced hypertension presenting with life-threatening thrombocytopenia. Am. J. Obstet. Gynecol. 146, 756–761 (1983).
Jacobson, C. in Utah in Demographic Perspective (eds Martin, T.K., Heaton, T.B. & Bahr, S.J.) 165–179 (Signature Press, New York).
Taylor, D.J. The epidemiology of hypertension during pregnancy. In Handbook of Hypertension, Vol 10: Hypertension in Pregnancy (ed. Rubin P.C.) 223–240 (Elsevier, Amsterdam, 1988).
Musey, V.C. et al. Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens. J. clin. Endocrin. Metab. 64, 111–118 (1987).
Wang, D.Y. et al. The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women. Eur. J. Cancer clin. Oncol. 24, 1225–1231 (1988).
American College of Obstetrics and Gynecology Pregnancy induced hypertension. Technical Bulletin, 91 (1986).
Sibai, B.M. et al. Maternal-perinatal outcome associated with the syndrome of hemolysis elevated liver enzymes and low platelets in severe preeclampsia-eclampsia. Am. J. Obstet. Gynecol. 155, 501–506 (1986).
Plouin, P.F., Chatellier, G., Guyenne, T.T., Vincent, N. & Corvol, P. Recent advances in the clinical study of the renin system. Reference values and conditions of validity. Presse Med. 18, 917–921 (1989).
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Ward, K., Hata, A., Jeunemaitre, X. et al. A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 4, 59–61 (1993). https://doi.org/10.1038/ng0593-59
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DOI: https://doi.org/10.1038/ng0593-59
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