title: Role of co-inherited Gilbert syndrome on hyperbilirubinemia in Indian beta thalassemia patients.
abstract: BACKGROUND
  Gilbert syndrome is characterized by mild unconjugated hyperbilirubinemia. The high levels of bilirubin could be related to the co-inheritance of Gilbert syndrome determined either by mutations of the coding region or by variation in the (TA)n motifs of the promoter region of the bilirubin UGT1A1 gene. The co-inheritance of Gilbert syndrome has been reported to elevate bilirubin levels in beta thalassemia and sickle cell disease patients. Aim In this study, we have tried to investigate whether the variability in serum bilirubin levels found in transfusion-dependent beta thalassemia, beta thalassemia intermedia, and heterozygous beta thalassemia individuals could be related to the coexistence of Gilbert syndrome.
  
  
  METHODS
  The promoter region (TA)n motifs of the bilirubin UGT1A1 gene were analyzed in 104 beta thalassemia individuals. The control group consisted of 50 healthy individuals.
  
  
  RESULTS
  The analysis of the UGT1A1 promoter showed three (TA) motifs: (TA)5, (TA)6, and (TA)7. The frequency of genotype (TA)7/(TA)7 did not differ significantly between the groups studied. A significant difference was observed in mean serum bilirubin levels between individuals showing (TA)7/(TA)7 and (TA)6/(TA)6 genotypes and also between (TA)7/(TA)7 and (TA)6/(TA)7 genotypes among all groups studied. According to the beta genotype, no differences were observed between mean serum bilirubin levels in the three groups (β(+)/β(+), β(0)/β(+), and β(0)/β(0)).
  
  
  CONCLUSIONS
  These results indicate that the (TA)7/(TA)7 configuration is one of the factors responsible for hyperbilirubinemia and, therefore, seems to interfere with the clinical expression of homozygous beta thalassemia. This emphasizes the role played by co-inherited modifying genes on clinical heterogeneity of monogenic disorders.
authors.forename: Pooja S
authors.initials: PS
authors.lastname: Dabke
authors.forename: Roshan B
authors.initials: RB
authors.lastname: Colah
authors.forename: Kanjaksha K
authors.initials: KK
authors.lastname: Ghosh
authors.forename: Anita H
authors.initials: AH
authors.lastname: Nadkarni
mesh_terms: D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D018900:Dinucleotide Repeats / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D005878:Gilbert Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000150:complications / Q000235:genetics*; D007194:India; D009154:Mutation; D059372:Nucleotide Motifs / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications / Q000235:genetics*; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
keywords: (TA)n repeats; Beta thalassemia; Bilirubin levels; Gilbert syndrome