Andrei Ivanov1, Elena Semenova2. 1. Human Genetics Department, Saint-Petersburg State University Hospital, 154, Fontanka River Embankment, St.Petersburg, 198103, Russia. 2. Division of Molecular and Radiation Biophysics, National Research Center "Kurchatov Institute" B.P.Konstantinov St Petersburg Nuclear Physics Institute, Gatchina, 188300, Russia.
Abstract
BACKGROUND/ OBJECTIVES: Gilbert's syndrome (GS) is a hereditary pathology that affects approximately 10% of the world's population. In most cases, GS is associated with the UGT1A1∗28 polymorphism of UGT1A1 gene coding the enzyme bilirubin uridine diphosphate glucuronosyltransferase (UGT-1A) which plays a key role in the bilirubin metabolism. The presence of an additional TA repeat in the TATA box of the UGT1A1 gene promoter (the allelic variant of 7TA, abbreviated as UGT1A1∗28) leads to a significant decrease in the enzymatic activity of UGT-1A in the liver and to decrease in glucuronidation process as a consequence. The aim of the study is to estimate the prevalence of the 6TA/6TA, 6TA/7TA, and 7TA/7TA genotypes of UGT1A1 promoter and to analyze the effect of these variants on bilirubin levels in healthy men in North-West Russia and patients with a clinical diagnosis of GS. METHODS: Genotyping of the UGT1A1 ∗28 (rs8175347) polymorphism was carried out by real-time PCR. RESULTS: The results obtained indicate an increased probability of GS developing in residents of the North-West region of Russia compared with other representatives of the Caucasians. CONCLUSIONS: Despite the fact that the level of serum bilirubin increases with the rise in the number of additional TA dinucleotides in the UGT1A1 gene promoter tests of clinical manifestations only (jaundice, fatigue, sleep disturbances, nausea, belching, and so on) and increased bilirubin levels in patients with normal liver function do not allow unequivocally diagnose GS. UGT1A1∗28 genotyping should be used as a prognostic risk factor for such pathology development.
BACKGROUND/ OBJECTIVES: Gilbert's syndrome (GS) is a hereditary pathology that affects approximately 10% of the world's population. In most cases, GS is associated with the UGT1A1∗28 polymorphism of UGT1A1 gene coding the enzyme bilirubin uridine diphosphate glucuronosyltransferase (UGT-1A) which plays a key role in the bilirubin metabolism. The presence of an additional TA repeat in the TATA box of the UGT1A1 gene promoter (the allelic variant of 7TA, abbreviated as UGT1A1∗28) leads to a significant decrease in the enzymatic activity of UGT-1A in the liver and to decrease in glucuronidation process as a consequence. The aim of the study is to estimate the prevalence of the 6TA/6TA, 6TA/7TA, and 7TA/7TA genotypes of UGT1A1 promoter and to analyze the effect of these variants on bilirubin levels in healthy men in North-West Russia and patients with a clinical diagnosis of GS. METHODS: Genotyping of the UGT1A1 ∗28 (rs8175347) polymorphism was carried out by real-time PCR. RESULTS: The results obtained indicate an increased probability of GS developing in residents of the North-West region of Russia compared with other representatives of the Caucasians. CONCLUSIONS: Despite the fact that the level of serum bilirubin increases with the rise in the number of additional TA dinucleotides in the UGT1A1 gene promoter tests of clinical manifestations only (jaundice, fatigue, sleep disturbances, nausea, belching, and so on) and increased bilirubin levels in patients with normal liver function do not allow unequivocally diagnose GS. UGT1A1∗28 genotyping should be used as a prognostic risk factor for such pathology development.
Authors: Ursula Ehmer; Tim O Lankisch; Thomas J Erichsen; Sandra Kalthoff; Nicole Freiberg; Michael Wehmeier; Michael P Manns; Christian P Strassburg Journal: J Mol Diagn Date: 2008-10-02 Impact factor: 5.568