ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy.
ABSTRACT To evaluate the nature and frequency of ATP-binding cassette subfamily B member 4 (ABCB4) gene variants in a series of French patients with intrahepatic cholestasis of pregnancy (ICP).
In this prospective study, the entire ABCB4 gene coding sequence was analysed by DNA sequencing in 50 unrelated women with ICP defined by pruritus and raised serum alanine aminotransferase activity or bile acid concentration, with recovery after delivery. Genomic variants detected in patients with ICP were sought in 107 control pregnant women. Patients with ICP and controls were of Caucasian origin.
Eight genomic variants were observed. One nonsense mutation (p.Arg144Stop) and two missense mutations (p.Ser320Phe and p.Thr775Met) were revealed each in one heterozygous patient. A third missense mutation (p.Arg590Gln) was detected in three heterozygous patients and in two homozygous patients also homozygous for a particular haplotype of three single-nucleotide polymorphisms (c.175C>T, c.504T>C, c.711A>T). The chromosomal frequency of the p.Arg590Gln variant was significantly different between the ICP and control group (7.0% vs 0.5%; p = 0.0017; OR 16.03, 95% CI 1.94 to 132.16). An association was also found between allele T of the c.504T>C silent nucleotide polymorphism and ICP (68.0% vs 53.7%; p = 0.017; OR 1.83, 95% CI 1.08 to 3.11). The chromosomal frequency of the p.Arg652Gly variant did not differ between the ICP and control group (p = 0.40).
This study shows that 16% of Caucasian patients with ICP bear ABCB4 gene mutations, and confirms the significant involvement of this gene in the pathogenesis of this complex disorder.
Article: Atypical causes of cholestasis.[Show abstract] [Hide abstract]
ABSTRACT: Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have "silent" progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury.
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ABSTRACT: There is no consistent definition of the term prurigo and a clear classification is unavailable. Definition of the current forms of prurigo and a new approach to a specific classification. Review of the types of prurigo as presented in current textbooks and publications. Pruritus is the main symptom of prurigo and shows an intensely pruritic papule or nodule as the main efflorescence. The term prurigo is not only used for secondary lesions, but also for primary dermatoses. The different forms of prurigo obtain their names depending on etiology, onset and duration of lesions or the clinical appearance. The term prurigo has not been used consistently. A revision of the classification with a clear distinction between primary dermatoses and secondary lesions seems reasonable. In secondary prurigo, a clinical classification and the cause should be mentioned.Der Hautarzt 08/2014; 65(8):684-90. DOI:10.1007/s00105-014-2753-z · 0.54 Impact Factor
Article: La cholestase gravidique[Show abstract] [Hide abstract]
ABSTRACT: Cholestasis of pregnancy presents with pruritus, sometimes incapacitating, less frequently by jaundice. It occurs during the second or third trimester. Its prevalence in France is of the order of 1 per 100 pregnancies. It is slightly more frequent during twin pregnancies. Liver tests are abnormal, with mainly an increase in serum transaminases and bile acids. Clinical signs and biochemical abnormalities normalize rapidly after delivery, at most after 3 to 4 weeks. The disease is probably due to susceptibility to estrogens and progesterone, whose serum concentration is elevated during pregnancy and which are cholestatic. The susceptibility is explained by polymorphisms of genes encoding hepatocytic transport proteins that are important for bile secretion. Besides disturbing pruritus, maternal prognosis is good. Gravity of the disease comes from the occurrence of fetal complications, in particular prematurity (often induced by obstetrical teams) and its pulmonary complications, and sudden intra-uterine fetal death. Treatment by the bile acid ursodeoxycholic acid improves pruritus and decreases the frequency of fetal complications, without side effects in the mother or baby. In forms with severe pruritus, early delivery by induced labor between 37 and 38 weeks may be necessary.La Revue Sage-Femme 06/2014; DOI:10.1016/j.sagf.2014.05.002