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

Abstract

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.

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy

“…This adds to previous reports of genetic associations found between autosomal fetal but not maternal variants and gestational hypertension in small, unreplicated studies 22,23 and variable associations between maternal blood pressure and interactions between fetal sex and maternal variants 24–26 . Our results are consistent with the suggestion that the fetal genome is able to influence maternal blood pressure in pregnancy 7,8 , although they are associations rather than demonstrating causality. When the alleles from these variants were amalgamated as a composite score there were significant associations demonstrated with each of three maternal blood pressure readings taken across the second half of pregnancy in our Cambridge cohorts.…”

“…It has been suggested that fetal genes may influence maternal metabolism and physiology 6 and we hypothesised that fetal growth genes in particular, may influence a mother’s risk of developing gestational hypertension and gestational diabetes 7,8 . Consistent with this, in the Swedish Birth and Multi-Generation Registries 20% of the variability in the risk for preeclampsia could be attributed to fetal genetic effects 9 .…”

Markers of Insulin Sensitivity in 12-Year-Old Children Born from Preeclamptic Pregnancies

“…2 Preeclampsia may recur across generations, and the fetal genotype (both maternal and paternal factors) contributes to the risk. 4,5 It is hypothesized that the pathophysiological events proceed in 2 phases. In early pregnancy, the placental function is probably disturbed by abnormal maternal immune responses to the trophoblast.…”

Independent Maternal and Fetal Genetic Effects on Midgestational Circulating Levels of Environmental Pollutants

“…Based on previous evidence that fetal genotypes may affect processes that alter pre- and postnatal maternal physiology (Liu et al 2015a; Petry et al 2007, 2014), we hypothesized that the circulating levels of maternal organohalogens could also be influenced by fetal genetic factors that might play an active role in controlling the toxicant disposition between mother and fetus. Surprisingly, we found that the heritability and genetic correlation results for midgestational levels of BB-153, BDE-47, -99, -100, -153, and Sum PBDE showed evidence for a higher impact of the total fetal genome-wide SNP-based genetic effects on maternal compound levels than the total maternal genetic effects, using equivalent datasets.…”