Angiotensinogen T235 expression is elevated in decidual spiral arteries.
Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.
Morgan
T
T
Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112, USA.
Craven
C
C
Nelson
L
L
Lalouel
J M
JM
Ward
K
K
D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000098:blood supply* / Q000378:metabolism
D012333:RNA, Messenger; D000808:Angiotensinogen; D012313:RNA