title: Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease.
abstract: Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients.
authors.affiliation: First Department of Medicine, University of Athens School of Medicine, Laikon General Hospital, 11527, Athens, Greece. vkalotyc@med.uoa.gr
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kalotychou
authors.forename: Katerina
authors.initials: K
authors.lastname: Antonatou
authors.forename: Revekka
authors.initials: R
authors.lastname: Tzanetea
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Loukopoulos
authors.forename: Yannis
authors.initials: Y
authors.lastname: Rombos
mesh_terms: D000595:Amino Acid Sequence; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000235:genetics*; D001663:Bilirubin / Q000097:blood; D005838:Genotype; D005878:Gilbert Disease / Q000150:complications / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006115:Greece; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology / Q000235:genetics; D011067:Poly dA-dT / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013789:Thalassemia / Q000097:blood / Q000150:complications / Q000235:genetics*; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D011067:Poly dA-dT; D000099148:UGT1A1 Enzyme