Angiotensinogen Thr235 variant is associated with abnormal physiologic change of the uterine spiral arteries in first-trimester decidua

• Published in: American journal of obstetrics and gynecology 1999, Vol.180 (1), p.95-102
• Main Authors: Morgan, Terry, Craven, Catherine, Lalouel, Jean-Marc, Ward, Kenneth
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Sequence - genetics; Angiotensinogen - genetics; Angiotensinogen Thr235; Arteries - abnormalities; Arteries - pathology; Biological and medical sciences; Decidua - blood supply; Diseases of mother, fetus and pregnancy; Female; Genetic Variation - physiology; Gynecology. Andrology. Obstetrics; Homozygote; Humans; Image Processing, Computer-Assisted; Medical sciences; physiologic change; preeclampsia; Pregnancy; Pregnancy Trimester, First - physiology; Pregnancy. Fetus. Placenta; Reference Values; Uterus - blood supply
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/S0002-9378(99)70156-0

Objective: The angiotensinogen Thr235 polymorphism associated with preeclampsia is tightly linked to a mutation in the angiotensinogen promoter A(-6), which may lead to elevated expression in decidual spiral arteries. We hypothesize that locally elevated angiotensin II levels play a role in failed physiologic change leading to preeclampsia. Our objective was to determine whether spiral artery morphologic characteristics were different in first-trimester decidual samples from women homozygous for the angiotensinogen Thr235 allele and women homozygous for the normal angiotensinogen Met235 allele. Study Design: We used quantitative histologic analysis to study 1266 spiral artery cross-sections in decidual samples obtained from normal pregnancies (n = 53) terminated at 8 weeks' gestation. To define vessel characteristics before pregnancy-induced remodeling, we also examined 60 arteries in nonpregnant endometrial control samples (n = 5). We measured the aspect ratio, media area, and external diameter of each cross-section with Image-Pro plus software. Maternal angiotensinogen genotypes were determined by means of mutagenically separated polymerase chain reaction. Average spiral artery morphologic measurements were compared between genotypes with the Student t test. Results: The media area/external diameter ratio was lower in decidual samples than in endometrial samples ( P < .0001), consistent with pregnancy-induced physiologic changes. Women homozygous for the angiotensinogen Thr235 allele (n = 11) had a greater area/diameter ratio than did women homozygous for the normal angiotensinogen Met235 allele (n = 11, P < .05). Samples from heterozygous women (n = 31) had intermediate values. Conclusion: Our results suggest that the angiotensinogen Thr235 allele predisposes women toward abnormal physiologic change, potentially beginning the cascade of events leading to preeclampsia. (Am J Obstet Gynecol 1999;180:95-102.)