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Genetic differences in protein key to pregnancy may help explain preterm birth rates

Genetic diversity in the receptor for a key reproductive hormone may help explain why some populations have higher rates of preterm birth than others.

Genetic diversity in the receptor for a key reproductive hormone may help explain why some populations have higher rates of preterm birth than others, according to a new Stanford study published in The American Journal of Human Genetics.

The hormone, progesterone, helps maintain pregnancy. The study focused on its receptor, which activates various physiological processes in pregnant women, such as keeping the uterine muscle from contracting. Changes in the progesterone receptor near the end of pregnancy also help trigger labor.

The Stanford researchers wondered if the progesterone receptor gene could provide clues about premature birth rates in different populations. Using data from the 1000 Genomes Project, they looked for differences in the gene between women of three ethnic ancestries. Women with Han Chinese ancestry had a version of the gene that appears to protect them from premature delivery.

From our press release:

Because progesterone and its receptor are so important for pregnancy, the results were unexpected. 'People have thought everyone should have a similar version of the progesterone receptor. But our study showed that we have different versions -- that there is diversity between individuals and between populations,' said Jingjing Li, PhD, an instructor of pediatrics at Stanford and the paper's lead author. 'It really surprised us.'

Women with European or African ancestry had much more variation in the gene, suggesting relatively recent divergence in the evolution of the gene between populations. Further, the gene version that protected women of East Asian ancestry from premature deliveries didn't have the same effect in a group of African-American mothers the team also studied. Again, from the press release:

The study's underlying message is that genes that are helpful in one environment may not help in another, [said the study's co-senior author, Gary Shaw, PhD.] 'Complex conditions such as prematurity are not likely caused completely environmentally or completely genetically; it's the confluence of genes and environment that makes the difference in risk,' he said.

Progesterone is sometimes given to pregnant women who have had prior preterm births to try to prevent another early delivery, but it doesn't always work, and no one knows why. Next, the researchers want to see if genetic differences in the receptor might explain that mystery.

Photo by Sara Neff

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