Genetic Factors Associated With Liver Disease in Pregnancy Identified

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver condition that occurs during pregnancy and is characterised by a disruption in the normal flow of bile from the liver. A new international study has identified a strong link between the genetic susceptibility to ICP and the body’s ability to regulate bile acids and metabolise lipids and cholesterol. The findings open up new avenues for research into maternal health and pregnancy-related liver diseases.

Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.2–2% of pregnant women and typically develops after 30 weeks of gestation. As the most common symptom is severe itching of the palms and the soles of the feet, the condition can often be identified during routine antenatal care. The diagnosis is confirmed by elevated liver enzyme levels and increased concentrations of bile acids in the blood. Although the condition usually resolves after delivery, it is associated with an increased risk of complications, including preterm birth and stillbirth.

Previous research has shown that certain genetic factors play an important role in susceptibility to ICP, but many of the underlying biological mechanisms have remained unclear.

A recent international study sheds new light on these mechanisms. The study combined extensive genetic data from more than 4,700 women with a history of ICP and a control group of over 436,000 women from Finland, Iceland, Estonia and Denmark.

“We identified a total of 26 genetic regions associated with the condition, including ten that have not been reported previously. The genes located in these regions influence how the liver processes bile acids, fats and cholesterol. This supports the idea that the underlying cause of ICP is a disruption in liver metabolism, triggered by hormonal changes during pregnancy,” says Postdoctoral Research Fellow Jaakko Tyrmi, who is affiliated with both Tampere University and the University of Oulu.

The risk of ICP is also linked to other conditions

In addition to identifying new genetic risk factors for ICP, the researchers investigated other conditions associated with this disorder. Women with a history of ICP were found to have an increased risk of developing diseases of the liver and bile ducts, including fatty liver disease, gallstones and inflammation of the bile ducts. They also had a higher risk of certain autoimmune diseases – such as Crohn’s disease – as well as thyroid disorders and type 2 diabetes.

“Our analyses also suggested a possible shared genetic basis between ICP and pancreatitis, which is inflammation of the pancreas, meaning that the same genetic susceptibility may increase the risk of both conditions. This is a new discovery that, to our knowledge, has not been reported previously. However, further studies are needed to better understand this connection,” says Tyrmi.

The findings hold promise for identifying at-risk groups, improving diagnosis and treatment, and supporting the early identification of related conditions.