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The potential impact of the fetal genotype on maternal blood pressure during pregnancy

Petry, Clive J.a; Beardsall, Kathryna,b; Dunger, David B.a,c

doi: 10.1097/HJH.0000000000000212
Reviews

The heritability of pregnancy-induced hypertension (encompassing both gestational hypertension and preeclampsia) is around 0.47, suggesting that there is a genetic component to its development. However, the maternal genetic risk variants discovered so far only account for a small proportion of the heritability. Other genetic variants that may affect maternal blood pressure in pregnancy arise from the fetal genome, for example wild-type pregnant mice carrying offspring with Cdkn1c or Stox1 disrupted develop hypertension and proteinuria. In humans, there is a higher risk for preeclampsia in women carrying fetuses with Beckwith–Wiedemann syndrome (including those fetuses with CDKN1C mutations) and a lower risk for women carrying babies with trisomy 21. Other risk may be associated with imprinted fetal growth genes and genes that are highly expressed in the placenta such as GCM1. This article reviews the current state of knowledge linking the fetal genotype with maternal blood pressure in pregnancy.

aDepartment of Paediatrics, University of Cambridge

bNeonatal Unit, Cambridge University Hospitals NHS Foundation Trust

cMedical Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK

Correspondence to Dr Clive J. Petry, Department of Paediatrics, Box 116, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. Tel: +44 1223 762945; fax: +44 1223 336996; e-mail: cjp1002@cam.ac.uk

Abbreviations: AGTR2, angiotensin II receptor type 2; CDKN1C, cyclin-dependent kinase inhibitor 1C; CI, confidence interval; ERAP2, endoplasmic reticulum aminopeptidase 2; GCM1, glial cells missing; drosophila; homologue of; GWAS, genome-wide association study; HELLP, haemolysis; elevated liver enzymes and low platelets; HLA, human leucocyte antigen; IGF2, insulin-like growth factor 2; KCNQ1OT1, potassium channel, voltage-gated, KQT-like subfamily, member 1-overlapping transcript 1; KDR, kinase insert domain receptor; KIR, killer immunoglobulin receptor; STOX1, storkhead box 1; TGFB3; transforming growth factor-β3

Received 19 December, 2013

Revised 17 March, 2014

Accepted 18 March, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins