Clinical

Polymorphism boosts risk of obstetric cholestasis

Last Updated: 2007-02-27 13:00:39 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - The severe form of intrahepatic cholestasis of pregnancy is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene, German and Swedish researchers report in the February issue of Gut.

"Obstetric cholestasis is not rare; about 1% of pregnancies are affected," senior investigator Dr. Frank Lammert told Reuters Health. "The main symptom is itching in late pregnancy."

Dr. Lammert, of the University of Bonn, and colleagues note that as well as pruritus, there are raised serum bile acid levels and increased fetal risk. Mutations of the ABCB4 gene, they add, have been identified in a small proportion of patients with cholestasis of pregnancy.

To investigate further, the researchers conducted genetic analysis in 52 pregnant Swedish women with elevated bile acid levels and 52 matched unaffected Swedish women who acted as controls.

In contrast to the similarity of ABCB11 haplotypes for bile acid transporters, ABCB4 haplotypes differed significantly between the two groups, say the investigators, showing that the severe form of cholestasis of pregnancy is associated with the ABCB4 gene variants.

Specifically, haplotype ABCB4_5 occurred more often in cases. Haplotypes ABCB4_3 and ABCB4_7 were more common in controls.

"The genetic markers that we describe might help to identify patients with obstetric cholestasis who are at risk for developing complications such as premature delivery or fetal death," Dr. Lammert concluded.

Gut 2007;56:265-270.