title: Co-inherited Gilbert's syndrome: a factor determining hyperbilirubinemia in homozygous beta-thalassemia.
abstract: OBJECTIVE
  Patients with thalassemia major and intermedia show a marked variability of serum indirect bilirubin levels. In this paper we tested the hypothesis related to the variability of the glucuronidation bilirubin rate which depends on the configuration of the A(TA)nTAA motif of the UGT1*1 glucuronosyltransferase gene promoter.
  
  
  METHODS
  We studied the configuration of the A(TA)nTAA motif in 26 patients with thalassemia major and 34 with thalassemia intermedia.
  
  
  RESULTS
  In patients with thalassemia major and in those with thalassemia intermedia significantly higher bilirubin levels were found in patients with the (TA)7/(TA)7 genotype, than in those with the (TA)7/(TA)6 or (TA)6/(TA)6 genotype.
  
  
  CONCLUSIONS
  These results indicate that the (TA)7/(TA)7 genotype, the configuration found in patients with Gilbert's syndrome, is capable of modifying the clinical phenotype of homozygous beta-thalassemia. This is an example of the role played by co-inherited modifying gene(s) on the extent of clinical heterogeneity of monogenic disorders.
authors: Istituto di Clinica e Biologia dell'Età Evolutiva, Università degli Studi di Cagliari, Ospedale Regionale Microcitemie, Italy. renzo.galanello@mcweb.unica.it
authors: R
authors: R
authors: Galanello
authors: M D
authors: MD
authors: Cipollina
authors: C
authors: C
authors: Dessì
authors: N
authors: N
authors: Giagu
authors: E
authors: E
authors: Lai
authors: A
authors: A
authors: Cao
mesh_terms: D005878:Gilbert Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics*; D012307:Risk Factors; D013577:Syndrome; D017086:beta-Thalassemia / Q000235:genetics*