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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 16
Ward K, Hata A, Jeunemaitre X et al..
A molecular variant of angiotensinogen associated with preeclampsia.
Nat Genet.
1993;
4
59-61
- 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
- 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
- 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
- 20
National High Blood Pressure Education Program Working Group .
report on high blood pressure in pregnancy.
Am J Obstet Gynecol.
1990;
163
1689-1712
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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
