Intrahepatic cholestasis of pregnancy (IPC: Intrahepatic cholestasis of pregnancy) - Genes ABCB11 or ABCB4

Intrahepatic cholestasis of pregnancy (IPC) is a liver disease which, as its name suggests, is manifested in women in gestation period. Cholestasis is an alteration affecting the release of bile of liver cells. As a result, the bile builds up in the liver, affecting their function. This disease is usually evident in the third trimester of pregnancy. Bile flow returns to normal after delivery, and signs and symptoms of the disease disappear. However, they may return in subsequent pregnancies.

Affected women have itching in pregnancy. The itching usually starts on the palms of hands and soles of the feet and then spreads to other parts of the body. And sometimes women affected jaundice. Some studies have shown that women with intrahepatic cholestasis of pregnancy are more likely to develop gallstones at some point in their lives than women without the disease. This disease is associated with an increased risk of preterm birth and stillbirth. In addition, some children born to mothers with intrahepatic cholestasis of pregnancy have a slow heart rate and lack of oxygen during birth.

Changes in ABCB11 and ABCB4 genes can increase the likelihood of a woman developing the disease.

The ABCB11 gene (ATP-binding cassette, subfamily B-MDR / TAP, member 11), located on the long arm of chromosome 2 (2q24), belongs to the family of ABC genes (ATP-Binding tranporters cassette), and the family ATP (superfamily ATPase) gene. This gene encodes a bile salt export protein (BSEP: Bile Salt Export Pump) that moves bile salts of hepatocytes.

A common polymorphism in the gene ABCB11 is more often in women who develop the disease than women who do not. This modification results in an amino acid change in the protein encoded by the gene. Specifically, the amino acid valine is replaced by the amino acid alanine at position 444 of the protein (V444A). This change causes a reduction in the amount of protein in liver cells BSEP. In rare cases, a mutation in one copy of the gene is ABCB11 in women with intrahepatic cholestasis of pregnancy. A single mutation in this gene increases the risk of developing the disease. These mutations are likely to reduce the encoded amount or function of the protein BSEP. Studies show that hormones estrogen and progesterone (and those formed during distribution products), which are elevated during pregnancy, reduce further the role of BSEP, resulting in impaired secretion of bile and the signs and symptoms of the illness. However, many other factors probably contribute to the risk of developing this complex disorder. Mutations ABCB11 gene have been associated with other forms of liver disease called intrahepatic cholestasis familial progressive 2 (PFIC2) - see familial intrahepatic cholestasis progressive - and intrahepatic cholestasis benign type 2 recurring (BRIC2) - see benign recurrent intrahepatic cholestasis - .

The ABCB4 gene (also known as MDR3) (ATP-binding cassette, subfamily B-MDR / TAP, member 4), located on the long arm of chromosome 7 (7q21.1), it belongs to the family of ABC genes (ATP- binding cassette transporters) or family of ATP (superfamily ATPase) gene. This gene encodes a protein that moves phospholipids through the cell membrane of hepatocytes. Outside of hepatocytes, phospholipids bind bile acids. When there is an excess of free bile acids, without being bound to phospholipids not secreted by hepatocytes, can be toxic.

A single mutation in the gene ABCB4 results in a slight reduction in the amount of protein encoded ABCB4. As a result, in most cases enough protein is available to move a suitable amount of phospholipids in liver cells bind bile acids. Although the mechanism is unclear, the role of ABCB4 protein appears to be impaired during pregnancy, which can further reduce the movement of phospholipids in the bile. Lack of available phospholipids to bind bile acids causes an accumulation of toxic bile acids may alter liver function, including regulation of bile flow. Mutations in this gene have also been associated with familial progressive intrahepatic cholestasis type 3 (PFIC3) - see progressive familial intrahepatic cholestasis -.

Susceptibility to intrahepatic cholestasis of pregnancy is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to increase the risk of developing the disease. Some women with an altered gene do not develop the disease. Many other factors probably contribute to the risk of developing this complex pathology.

Tests in IVAMI: in IVAMI perform detection of mutations associated with intrahepatic cholestasis of pregnancy, by complete PCR amplification of the exons of ABCB11 and ABCB4, respectively, and subsequent sequencing genes.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).