Semin Thromb Hemost 2001; 27(2): 143-148
DOI: 10.1055/s-2001-14073
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Multivariate Analysis of Genetic and Acquired Factors; T235 Variant of the Angiotensinogen Gene Is a Potent Independent Risk Factor for Preeclampsia

Gen Kobashi1 , Koichi Shido1 , Akira Hata1 , Hideto Yamada2 , Emi-Hirayama Kato2 , Masao Kanamori3 , Seiichiro Fujimoto2 , Kiyotaro Kondo4
  • 1Department of Preventive Medicine, Hokkaido University Graduate School of Medicine, Sappor, Japan
  • 2Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • 3Department of Public Health, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • 4The University of the Air, Chiba, Japan
Further Information

Publication History

Publication Date:
31 December 2001 (online)

ABSTRACT

Preeclampsia is known to be a multifactorial disease. Recently, the angiotensinogen gene has been shown to be a candidate gene that could be related to preeclampsia, and acquired factors such as lifestyle during pregnancy have also been considered to be risk factors. The aim of this study was to investigate the interrelations among the angiotensinogen gene and various acquired risk factors in preeclampsia. Fifty-eight primiparous patients with preeclampsia were compared with 164 normal primiparous controls. A variant of the angiotensinogen gene (M235T) was analyzed along with the acquired factors obtained from both medical records and a questionnaire consisting of 98 questions. Univariate analysis disclosed 11 factors that were significantly associated with preeclampsia (P < .05). Multivariate analysis revealed four significant independent factors: ``prepregnancy high body mass (body mass index ≥ 24),'' ``T235 homozygotes of the angiotensinogen gene,'' ``mentally stressful condition during pregnancy,'' and ``salty dishes preferred during pregnancy.'' The odds ratios of the four factors were 6.2, 2.5, 3.0 and 2.6, respectively, in a multiple logistic model. Our results support the concept that T235 of the angiotensinogen gene is a potent, independent risk factor for preeclampsia, as well as other lifestyle-related risk factors.

REFERENCES

  • 1 Jeunemaitre X, Soubrier F, Kotelevtsev Y V. Molecular basis of human hypertension: role of angiotensinogen.  Cell . 1992;  71 169-180
  • 2 Hata A, Namikawa C, Sasaki M. Angiotensinogen as a risk factor for essential hypertension in Japan.  J Clin Invest . 1994;  93 1285-1287
  • 3 Ward K, Hata A, Jeunemaitre X. A molecular variant of angiotensinogen associated with preeclampsia.  Nat Genet . 1993;  4 59-61
  • 4 Kobashi G, Hata A, Shido K. Association of a variant of the angiotensinogen gene with pure type of hypertension in pregnancy in the Japanese: implication of a racial difference and significance of an age factor.  Am J Med Genet . 1999;  86 232-236
  • 5 Moregan L, Baker P, Pipkin F B, Kalsheker N. Pre-eclampsia and the angiotensinogen gene.  Br J Obstet Gynaecol . 1995;  102 489-490
  • 6 Inoue I, Nakajima T, Williams C S. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.  J Clin Invest . 1997;  99 1786-1797
  • 7 Morgan T, Craven C, Lalouel J M, Ward K. Angiotensinogen Thr235 variant is associated with abnormal physiologic change of the uterine spinal arteries in first-trimester decidua.  Am J Obstet Gynecol . 1999;  180 95-102
  • 8 Chesley L C. History and epidemiology of preeclampsia-eclampsia.  Clin Obstet Gynecol . 1984;  27 801-820
  • 9 Eskenazi B, Fenster L, Sidney S. A multivariate analysis of risk factors for preeclampsia.  JAMA . 1991;  266 237-241
  • 10 National High Blood Pressure Education Program Working Group. Report on high blood pressure in pregnancy (Consensus Report).  Am J Obstet Gynecol . 1990;  163 1689-1712
  • 11 Russ A P, Maerz W, Ruzicka V, Stein U, Gross W. Rapid detection of the hypertension-associated Met235Thr allele of the human angiotensinogen gene.  Hum Mol Genet . 1993;  2 609-610
  • 12 Jaspers W J, de Jong A P, Mulder A W. Decrease of angiotensin sensitivity after bed rest and strongly sodium-restricted diet in pregnancy.  Am J Obstet Gynecol . 1983;  145 792-796
  • 13 Millar J A. Salt and pregnancy-induced hypertension.  Lancet . 1988;  2 514
  • 14 Nabeshima K. Effect of salt restriction on preeclampsia.  Nippon Jinzo Gakkai Shi . 1994;  36 227-232
  • 15 Paarlberg K M, Vingerhoets A JM, Passchier J, Dekker G A, Van Geijn P H. Psychosocial factors and pregnancy outcome: a review with emphasis on methodological issues.  J Psychosom Res . 1995;  39 563-595
  • 16 Henzel B S, Bruer B, Poidevin L. A survey of the relation between certain common antenatal complications in primiparae and stressful life situations during pregnancy.  J Psychosom Res . 1961;  5 175-182
  • 17 Rofé Y, Goldberg J. Prolonged exposure to a war environment and its effects on the blood pressure of pregnant women.  Br J Med Psychol . 1983;  56 305-311
  • 18 Nisell H, Larsson G, Wager J. The relation between life stress and hypertensive complications during pregnancy.  Acta Obstet Gynaecol Scand . 1989;  68 423-427
  • 19 Saurel-Cubizolles M J, Kaminski M, Du Mazaubrun C, Llado J, Estrynbehar M. High blood pressure during pregnancy and working conditions among hospital personnel.  Eur J Obstet Gynecol Reprod Biol . 1991;  40 29-34