Coexistence of Gilbert syndrome with hereditary haemolytic anaemias

J Clin Pathol. 2012 Jul;65(7):663-5. doi: 10.1136/jclinpath-2011-200580. Epub 2012 May 3.

Abstract

Background: Gilbert syndrome is an inherited disease characterised by mild unconjugated hyperbilirubinaemia caused by mutations in UGT1A1 gene which lead to decreased activity of UDP-glucuronosyltransferase 1A1. The most frequent genetic defect is a homozygous TA dinucleotide insertion in the regulatory TATA box in the UGT1A1 gene promoter.

Methods and results: 182 Polish healthy individuals and 256 patients with different types of hereditary haemolytic anaemias were examined for the A(TA)(n)TAA motif. PCR was performed using sense primer labelled by 6-Fam and capillary electrophoresis was carried out in an ABI 3730 DNA analyser. The frequency of the (TA)(7)/(TA)(7) genotype in the control group was estimated at 18.13%, (TA)(6)/(TA)(7) at 45.05% and (TA)(6)/(TA)(6) at 36.26%. There was a statistically significant difference in the (TA)(6)/(TA)(6) genotype distribution between healthy individuals and patients with glucose-6-phosphate dehydrogenase deficiency (p=0.041). Additionally, uncommon genotypes, (TA)(5)/(TA)(6), (TA)(5)/(TA)(7) and (TA)(7)/(TA)(8) of the promoter polymorphism, were discovered.

Conclusion: Genotyping of the UGT1A1 gene showed distinct distribution of the common A(TA)(n)TAA polymorphism relative to other European populations. Because of a greater risk of hyperbilirubinaemia due to hereditary haemolytic anaemia, the diagnosis of Gilbert syndrome in this group of patients is very important.

MeSH terms

  • Anemia, Hemolytic, Congenital / epidemiology*
  • Anemia, Hemolytic, Congenital / ethnology
  • Anemia, Hemolytic, Congenital / genetics*
  • Case-Control Studies
  • Comorbidity
  • Genotype
  • Gilbert Disease / epidemiology*
  • Gilbert Disease / ethnology
  • Gilbert Disease / genetics*
  • Glucuronosyltransferase / genetics
  • Humans
  • Poland
  • Polymorphism, Genetic / genetics
  • Prevalence

Substances

  • UGT1A1 enzyme
  • Glucuronosyltransferase