Vitamin D, Hypermethylation, & High Blood Pressure during Pregnancy

November 4, 2015

Nationally, there has been a vitamin D deficiency within the U.S. population. Insufficient levels of vitamin D have been associated with improper eating habits, lack of sun exposure and dark skin color. Some foods that are rich in vitamin D include fatty fish such as tuna and salmon and foods that are fortified with it. Beef liver, cheese and egg yolks are some foods that contain a little amount of vitamin D as well. The body uses vitamin D in a number of physiological responses, through the steps of gene regulation, to turn DNA into a protein and the communication between cells. Prior research shows that low vitamin D levels may be an important component in the development of high blood pressure during pregnancy, which is one symptom of preeclampsia. Preeclampsia is dangerous because it affects the arteries carrying blood to the placenta, disrupting the amount of oxygen and nutrients the baby receives. This function could lead to stunted growth, low birth weight or a preterm birth.  The research also shows that low levels of vitamin D before the middle of a woman’s pregnancy more than doubles the risk of developing preeclampsia. The link between vitamin D and the risk of preeclampsia is considered to be a result of the placenta containing a vitamin D endocrine system within it. This system shows that vitamin D metabolism has a critical part in the placenta with the development of a baby.

The present study examined the epigenetic changes in major placental genes (enzyme 1α-hydroxylase (CYP27B1), nuclear receptor region for vitamin D of the transcription site (VDR) and the retinoid X receptor (RXR) where vitamin D metabolism (the process of modifying a chemical for use in another reaction) is undergoing gene expression, in order to assess the genes associated with the cause of preeclampsia. There were 48 participants, who were all first time mothers in their first trimester, separated into two groups: those who developed high blood pressure (11 women with an average age of 25.3 years) and those who had a normal blood pressure (37 women with an average age of 24.2 years) during pregnancy. The data collected contained information regarding: pregnancy outcome, vitamin D intake, maternal vitamin D status, DNA methylation and protein expression. DNA methylation acts to alter gene expression in cells, in pregnancy, it allows the baby to develop. Protein expression is the formation of the material needed so development can occur.

The researchers found that with the exception of the lowest diastolic blood pressure in the second trimester, there were no differences in blood pressure between the two groups when comparing the maternal vitamin D status. There were also no differences found when comparing the two groups in respect to vitamin D intake. The researchers found that DNA methylation was increased in women who had high blood pressure of the enzyme 1α-hydroxylase (CYP27B1), nuclear receptor region for vitamin D of the transcription site (VDR) and the retinoid X receptor (RXR). Although no changes in protein expression were observed for the VDR or CYP27B1 proteins, the RXR protein expression was significantly reduced in those who had high blood pressure.

The researchers concluded that hypermethylation has a larger effect on pregnancy than low vitamin D levels in the development of preeclampsia. Hypermethylation is the increase activation of methylation. The hypermethylation at major placental genes that are involved with vitamin D signaling (messaging from the mother to the baby), with the addition of a reduced expression of RXR, are key components that indicate the risk of developing preeclampsia. Providers should ensure women who are at risk of preeclampsia are getting an adequate amount of vitamin D, to compensate for the limiting effects hypermethylation has on its transfer from mother to baby through the placenta. 

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Written by Gregory McDaniel, Visiting Student in Research.