Gilbert-Meulengracht's syndrome and pharmacogenetics: is jaundice just the tip of the iceberg?
Gilbert's syndrome is characterized by mild unconjugated nonhemolytic hyperbilirubinemia, without hepatic inflammation, fibrosis, chronic liver disease, or liver failure. It is readily diagnosed by genetic variants of the UGT1A1 gene, mainly UGT1A1*28, and is also associated with abnormalities of hepatobiliary transport and additional UGT1A gene variants. Apart from representing a potential risk factor in irinotecan and protease inhibitor therapy, it appears to exert protective effects in Hodgkin's lymphoma and cardiovascular disease. Gilbert's syndrome is part of a continuous spectrum of altered glucuronidation that extends to fatal Crigler-najjar disease. The complexity hidden behind this pharmacogenetic abnormality is of profound significance for drug development and therapy.
Strassburg
Christian P
CP
Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. strassburg.christian@mh-hannover.de
D003414:Crigler-Najjar Syndrome / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005878:Gilbert Disease / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000453:epidemiology; D007565:Jaundice / Q000150:complications / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme