A functional variant in ANGPT1 and the risk of pregnancies with hypertensive disorders and small-for-gestational-age infants.
Pregnancies complicated by pre-eclampsia and small-for-gestational-age (SGA) infants demonstrate impaired placental vascular remodelling. Angiopoietin-1 (ANG-1) is an angiogenic growth factor which regulates vascular integrity and remodelling. The TT genotype of angiopoietin 1 (ANGPT1) rs2507800 polymorphism has been associated with increased plasma ANG-1 levels compared with the AA genotype. We aimed to investigate the association between ANGPT1 rs2507800 polymorphism and pregnancies complicated by gestational hypertensive disorders and SGA infants. We also aimed to investigate whether the polymorphism was associated with abnormal uterine artery Doppler as a surrogate marker of impaired placental vascular remodelling. Genotyping data of 1361 nulliparous pregnant women, 1226 partners and 1190 infants were analysed. The prevalence of ANGPT1 rs2507800 TT genotype was reduced in women with pre-eclampsia [P = 0.01, adjusted odds ratio (aOR), 0.5; 95% confidence interval (CI), 0.3-0.9], hypertensive SGA (P = 0.04, aOR, 0.5; 95% CI, 0.2-0.9) and SGA with abnormal uterine artery Doppler (P = 0.009, aOR, 0.4. 95% CI, 0.2-0.8) compared with women with uncomplicated pregnancy. The prevalence of maternal ANGPT1 rs2507800 TT genotype was reduced in women with increased uterine artery resistance index (P = 0.03, aOR, 0.7; 95% CI, 0.5-0.9) and bilateral notching of the uterine arteries (P = 0.004, aOR, 0.6; 95% CI, 0.4-0.9). These results remained significant after correcting for multiple testing. Maternal ANGPT1 rs2507800 TT genotype is associated with a reduced risk for pre-eclampsia, hypertensive SGA and abnormal uterine artery Doppler. These findings suggest that the TT genotype may protect against these pregnancy disorders by increasing ANG-1 production at the maternal-fetal interface. The ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications. TRIAL REGISTRY NAME: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth.
Discipline of Obstetrics and Gynaecology, Research Centre for Reproductive Health,  University of Adelaide, Adelaide,  Australia.
Prabha H
PH
Andraweera
Gustaaf A
GA
Dekker
Steven D
SD
Thompson
Robyn A
RA
North
Lesley M E
LM
McCowan
Claire T
CT
Roberts
D000328:Adult; D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D009520:New Zealand; D010922:Placenta Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011446:Prospective Studies; D012306:Risk; D013021:South Australia; D014463:Ultrasonography; D055988:Uterine Artery / Q000000981:diagnostic imaging / Q000473:pathology; D055815:Young Adult
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D015415:Biomarkers