Maternal hypertension-related genes affect the fetal growth via placenta

Abstract

Low birth weight is associated with the development of cardio-metabolic diseases later in life1-4. A recent Mendelian Randomization Study concluded that the susceptibility of low-birth-weight infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother, and not to an unfavorable intrauterine environment5. Therein, it has been assumed that low birth weight is caused by maternal hypertension5,6, although there is no evidence to support such a linear relationship. In the present study, we have noted that most of blood pressure SNPs are related to vascular regulation7-9 and found that the relationship between maternal blood pressure-increasing polygenic score and reduction of offspring birth weight is mediated by a reduced growth of the placenta but not by the mother's high blood pressure. This suggests that the risk of hypertension of low-birth-weight infants may result from a poor placental environment.

Genetic variation in placental insufficiency: What have we learned over time?

“…However, these alleles only influenced later offspring blood pressure if they were inherited, highlighting the direct effect of fetal genetics. A similar association between maternal genotype and offspring birth weight was observed in Japan; however, this association was mediated by placental weight (Sato et al, 2021). Interestingly, a subset of genetic variants associated with birth weight have also shown parent-of-origin specific effects, in which maternal effects on birth weight were through glucose metabolism and blood pressure regulation (Juliusdottir et al, 2021).…”

“…Currently, researchers are studying the combined effect of multiple variants, through an approach known as the polygenic-risk-score (PRS). The placenta has been found to mediate the effect of maternal hypertension genes on offspring birth weight (Sato et al, 2021).…”