Abstract for presentation at 11th International Congress of Human Genetics

High Prevalence of Hypomorphic UGT1A1 Haplotypes in the Singapore Population

  • Miss Youyou Zhou, National University of Singapore, Singapore
  • Miss Siew Yee Ng, National University of Singapore, Singapore
  • Dr Cindy Hia, National University Hospital, Singapore
  • Dr Le Ye Lee, National University Hospital, Singapore
  • Dr Mohammad Iqbal Abu Sayeed, National University Hospital, Singapore
  • Dr Kah Tzay Low, National University Hospital, Singapore
  • Dr Yap Seng Chong, National University of Singapore, Singapore
  • Denise Goh, National University of Singapore, Singapore

    • Background: Uridine Diphosphate Glucuronyltransferase 1A1 (UGT1A1) is an enzyme critical in the detoxification of bilirubin, irinotecan and other substrates. Decreased UGT1A1 enzyme activity is associated with increased risk for neonatal jaundice and irinotecan induced leukopaenia and diarrhoea.
    Aims: Our aim is to ascertain the prevalence of hypomorphic haplotypes in the Singapore population.
    Methods: Newborn babies were prospectively recruited after informed consent was obtained from the parents antenatally. DNA was extracted from cord blood. The promoter, exons 1 to 4, coding region of exon 5 and their flanking intronic regions of UGT1A1 were amplified and sequenced. A hypomorphic haplotype was defined as a mutation known or predicted to result in a gene product with reduced function.
    Results: Ninety-four Chinese, 72 Indian and 87 Malay babies were recruited. Twelve haplotypes were identified with four being novel; Five haplotypes were known to have reduced function while the four novel ones were predicted to have decreased function. The prevalence of these 9 hypomorphic haplotypes was high; 34.0% had one hypomorphic haplotype and 12.3% had two hypomorphic haplotypes. The prevalence was also different between ethnic groups, with 46.8% Chinese, 63.9% Indian and 31.0% Malay babies having at least one hypomorphic haplotype (Chi square test p<0.05).
    Conclusions: The prevalence of hypomorphic haplotypes in the Singapore population was high. This may explain the higher incidence of neonatal jaundice seen in local babies, a hypothesis being tested by a prospective study. Pharmacokinetic studies of irinotecan are also being carried out to establish safe, effective doses for patients with hypomorphic UGT1A1 haplotypes.

    Conference Organiser - ICMS Pty Ltd