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Semin Thromb Hemost 2005; 31(3): 346-350
DOI: 10.1055/s-2005-872442
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Preeclampsia in Japanese Patients

Gen Kobashi1 , 2 , Akira Hata4 , Koichi Shido2 , Kaori Ohta2 , Hideto Yamada3 , Emi Hirayama Kato3 , Hisanori Minakami3 , Hiko Tamashiro2 , Seiichiro Fujimoto3 , Kiyotaro Kondo5
  • 1Assistant Professor, Division of Preventive Medicine, Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Sapporo, Japan
  • 2Division of Preventive Medicine, Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Sapporo, Japan
  • 3Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Sapporo, Japan
  • 4Department of Public Health, Asahikawa Medical College School of Medicine, Asahikawa, Japan
  • 5The University of the Air, Chiba, Japan
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Publication History

Publication Date:
28 July 2005 (online)

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ABSTRACT

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene (ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen (AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.

KEYWORDS

Preeclampsia - pregnancy - angiotensin-converting enzyme - polymorphism

REFERENCES

  • 1 Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.  J Clin Invest. 1990;  86 1343-1346
    CrossrefPubMedSearch in Google Scholar
  • 2 Tiret L, Rigat B, Visvikis S et al.. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-convertin enzyme (ACE) gene controls plasma ACE levels.  Am J Hum Genet. 1992;  51 197-205
    PubMedSearch in Google Scholar
  • 3 Cambien F, Poirier O, Lecerf L et al.. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.  Nature. 1992;  359 641-644
    CrossrefPubMedSearch in Google Scholar
  • 4 Oike Y, Hata A, Ogata Y, Numata Y, Shido K, Kondo K. Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction.  J Clin Invest. 1995;  96 2975-2979
    PubMedSearch in Google Scholar
  • 5 Uemura K, Nakura J, Kohara K, Miki T. Association of ACE I/D polymorphism with cardiovascular risk factors.  Hum Genet. 2000;  107 239-242
    PubMedSearch in Google Scholar
  • 6 Abbud Z A, Wilson A C, Cosgrove N M, Kostis J B. Angiotensin-converting enzyme gene polymorphism in systemic hypertension.  Am J Cardiol. 1998;  81 244-246
    CrossrefPubMedSearch in Google Scholar
  • 7 Higashimori K, Zhao Y, Higaki J et al.. Association analysis of the angiotensin coverting enzyme gene with essential hypertension in the Japanese population.  Biochem Biophys Res Commun. 1993;  191 399-404
    CrossrefPubMedSearch in Google Scholar
  • 8 Ishigami T, Iwamoto T, Tamura K et al.. Angiotensin I converting enzyme (ACE) gene polymorphism and essential hypertension in Japan. Ethnic difference of ACE genotype.  Am J Hypertens. 1995;  8 95-97
    CrossrefPubMedSearch in Google Scholar
  • 9 Tamaki S, Nakamura Y, Tsujita Y et al.. Polymorphism of the angiotensinogen converting enzyme gene and blood pressure in Japanese general population (the Shigaraki Study).  Hypertens Res. 2002;  25 843-848
    CrossrefPubMedSearch in Google Scholar
  • 10 Parente J V, Franco Jr J G, Greene L J, Meirelles R S, Martinez A R. Angiotensin-converting enzyme: serum levels during normal pregnancy.  Am J Obstet Gynecol. 1979;  135 586-589
    PubMedSearch in Google Scholar
  • 11 Oats J N, Pipkin F B, Symonds E M. Angiotensin-converting enzyme and the renin-angiotensin system in normotensive primigravid pregnancy.  Clin Exp Hypertens Res. 1982;  1 73-91
    PubMedSearch in Google Scholar
  • 12 Goldkrand J W, Fuentes A M. The relation of angiotensin-converting enzyme to the pregnancy-induced hypertension-preeclampsia syndrome.  Am J Obstet Gynecol. 1986;  154 792-800
    PubMedSearch in Google Scholar
  • 13 Rasmussen A B, Pedersen E B, Romer F K et al.. The influence of normotensive pregnancy and pre-eclampsia on angiotensin-converting enzyme.  Acta Obstet Gynecol Scand. 1983;  62 341-344
    PubMedSearch in Google Scholar
  • 14 Li J, Hu H Y, Zhao Y N. Serum angiotensin-converting enzyme activity in pregnancy-induced hypertension.  Gynecol Obstet Invest. 1992;  33 138-141
    PubMedSearch in Google Scholar
  • 15 Zhou N, Yu P, Chen J, Huang H, Jiang S. Detection of insertion/deletion polymorphism of angiotensin converting enzyme gene in preeclampsia.  Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1999;  16 29-31
    PubMedSearch in Google Scholar
  • 16 Ward K, Hata A, Jeunemaitre X et al.. A molecular variant of angiotensinogen associated with preeclampsia.  Nat Genet. 1993;  4 59-61
    CrossrefPubMedSearch in Google Scholar
  • 17 Kobashi G, Hata A, Shido K et al.. 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
    CrossrefPubMedSearch in Google Scholar
  • 18 Inoue I, Nakajima T, Williams C S et al.. 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
    PubMedSearch in Google Scholar
  • 19 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
    CrossrefPubMedSearch in Google Scholar
  • 20 National High Blood Pressure Education Program Working Group . report on high blood pressure in pregnancy.  Am J Obstet Gynecol. 1990;  163 1689-1712
    PubMedSearch in Google Scholar
  • 21 Tamakoshi A, Ishikawa S, Ojima T et al.. The guideline of informed consent in epidemiological studies, Ver. 1.0 Tokyo; Nihonijishinposya 2000: 1-27
    Search in Google Scholar
  • 22 Odawara M, Matsunuma A, Yamashita K. Mistyping frequency of the angiotensin-converting enzyme gene polymorphism and an improved method for its avoidance.  Hum Genet. 1997;  100 163-166
    PubMedSearch in Google Scholar
  • 23 Russ A P, Maerz W, Ruzicka V, Stein U, Gross W. Rapid detection of the hypertension-associated Met235→Thr allele of the human angiotensinogen gene.  Hum Mol Genet. 1993;  2 609-610
    PubMedSearch in Google Scholar
  • 24 Tamura T, Johanning G L, Goldenberg R L, Johnston K E, DuBard M B. Effect of angiotensin-converting enzyme gene polymorphism on pregnancy outcome, enzyme activity, and zinc concentration.  Obstet Gynecol. 1996;  88 497-502
    CrossrefPubMedSearch in Google Scholar
  • 25 Morgan L, Foster F, Hayman R et al.. Angiotensin-converting enzyme insertion-deletion polymorphism in normotensive and preeclamptic pregnancies.  J Hypertens. 1999;  17 765-768
    CrossrefPubMedSearch in Google Scholar
  • 26 Nalogowska-Glosnicka K, Lacka B, Zychma M et al.. Lack of relationship between angiotensinogen gene m235t polymorphism and gene insertion/deletion (I/D-intron 16) and Pst I RFLP (P/M-intron 7) polymorphisms of the angiotensin I converting enzyme (ACE) gene and the development of H-gestosis. Preliminary results.  Pol Arch Med Wewn. 1998;  100 19-26
    PubMedSearch in Google Scholar
  • 27 Kobashi G, Shido K, Hata A et al.. Multivariate analysis of genetic and acquired factors: T235 variant of angiotensinogen gene as a potent independent risk factor for preeclampsia.  Semin Thromb Hemost. 2001;  27 143-147
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Kawamoto R, Kohara K, Tabara Y, Miki T. An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis.  Hypertens Res. 2002;  25 875-880
    CrossrefPubMedSearch in Google Scholar

 Dr.
Gen Kobashi

Department of Health for Senior Citizens, Hokkaido University Graduate School of Medicine

N15 W7, Sapporo 060-8638, Japan

Email: genkoba@med.hokudai.ac.jp