Genetic Markers Linked to Preterm Birth Identified

Genetic Markers Linked to Preterm Birth Identified
Portrait of a woman in a striped dress holding her pregnancy bump.

Research led by the University of Chicago has discovered two genes, HAND2 and GATA2, that could influence whether a woman gives birth prematurely or not.

“These genes are both important transcription factors that regulate the expression of several other genes,” said Ivy Aneas, Ph.D., a research associate at the University of Chicago and one of the lead researchers involved in the study.

HAND2 mediates the effect of progesterone on the uterine epithelium while GATA2 is involved in stem cell maintenance.”

The researchers hope that these results may help clinicians predict whether preterm birth is a likely pregnancy outcome and plan accordingly.

Previous studies have suggested that there is a genetic element to preterm birth, but a lack of knowledge about gene expression in placental and endometrial cells has made it hard to pinpoint these connections more accurately.

“When you’re studying a disease, there are typically a lot of genetic and tissue resources available in public databases,” said co-senior researcher Carole Ober, Ph.D., a professor at the University of Chicago. “But pregnancy related conditions, like preterm birth, get much less attention or funding, and as a result pregnancy-relevant tissues are not well represented in those databases.”

To investigate this further, Aneas and colleagues tested endometrial cells attached to the placenta after birth for markers of gene expression. They collected transcriptome data by sequencing the RNA, searched for epigenetic modifications and evaluated chromatin structural changes. They then compared these results with genome wide association data from 56,384 women collected in a study looking at pregnancy duration.

As reported in the journal Science Advances, the team found two new genes linked with preterm birth — HAND2 and GATA2, which are involved in the process of ‘decidualization’ when the endometrial cells prepare for pregnancy and placenta formation by implanting into the uterine wall.

From the data the researchers collected, they think HAND2 is directly linked with gestational duration and in endometrial cells they think GATA2 is the target of nearby genetic variants linked with preterm birth. Neither of these genes have previously been linked with pregnancy length.

“The fact that we identified a link between these two genes and the duration of gestation suggests that their roles in pregnancy may be more important than previously anticipated,” said co-first author Noboru Sakabe, Ph.D., a researcher at the University of Chicago.

The researchers caution that they only analyzed one type of cell taken from three individuals so their results need to be replicated. The cells were also collected after birth, so they acknowledge there may be changes that occur during pregnancy that were not reflected here.

“Future studies that include fetal cells from the placenta and uterine or cervical myometrial cells could reveal additional processes that contribute to gestational duration and preterm birth, such as those related to fetal signaling and the regulation of labor,” write the authors.