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A Molecular Variant of Angiotensinogen Is Associated With Idiopathic Intrauterine Growth Restriction

Zhang, Xiu Quan MD, PhD; Varner, Michael MD; Dizon-Townson, Donna MD; Song, Francis MD; Ward, Kenneth MD

Obstetrics & Gynecology:
Original Research

OBJECTIVE: Intrauterine growth restriction has been associated with failed maternal physiologic changes such as abnormal spiral artery remodeling and reduced maternal blood volume. A polymorphism of angiotensinogen Thr235 has been considered a risk factor for preeclampsia. We genotyped maternal and fetal deoxyribonucleic acid (DNA) for angiotensinogen Thr235 to estimate whether the polymorphism is also a risk factor for intrauterine growth restriction.

METHODS: We examined maternal blood DNA in 174 patients with intrauterine growth restriction and 60 patients with both preeclampsia and intrauterine growth restriction. The control group comprised 400 consecutive cases of women with term pregnancies and infants with birth weight between the fifth and 95th percentiles. We also examined 162 DNA samples from fetal blood with intrauterine growth restriction for the Thr235 polymorphism, and 240 normal fetuses were used as the control group. The angiotensinogen genotype was determined using mutagenically separated polymerase chain reaction. The products were size fractionated on an agarose gel. Angiotensinogen genotypes were divided into three groups: MM (homozygous for angiotensinogen Met235 allele), TT (homozygous for angiotensinogen Thr235 allele), and MT (heterozygous).

RESULTS: Maternal genotyping revealed a significantly higher Thr235 allele frequency in intrauterine growth restriction (.60) and preeclampsia/intrauterine growth restriction (.63) than in the control group (.36) (P < .001). Fetal genotyping revealed a Thr235 allele frequency of .59 in intrauterine growth restriction fetuses, as compared with the control group (.38) (P < .001).

CONCLUSION: Maternal and fetal angiotensinogen Thr235 genotypes are associated with an increased risk of intrauterine growth restriction in our study population. The angiotensinogen Thr235 allele may predispose women to deliver growth-restricted fetuses.

In Brief

Women with the angiotensinogen Thr235 mutation are at increased risk for intrauterine growth restriction and pregnancy-induced hypertension.

Author Information

Departments of Obstetrics and Gynecology and Human Genetics, University of Utah, Salt Lake City, Utah.

Address reprint requests to: Kenneth Ward, MD, University of Utah School of Medicine, Department of Obstetrics and Gynecology, 50 North Medical Drive, RM 2B200, Salt Lake City, UT 84108; E-mail:

This study is supported by a grant from the National Institutes of Health, the National Heart, Lung, and Blood Institute (1R01-HD 32170-01).

The authors are grateful for the participation of the obstetric patients who delivered at the University of Utah Health Sciences Center. They also gratefully acknowledge the assistance of the medical and nursing staff of the Department of Obstetrics and Gynecology.

Received March 26, 2002. Received in revised form July 2, 2002. Accepted August 1, 2002.

© 2003 The American College of Obstetricians and Gynecologists