UGT1A1 (TA)n PROMOTER GENOTYPE:
DIAGNOSTIC AND POPULATION
PHARMACOGENETIC MARKER IN SERBIA Vukovic M, Radlovic N, Lekovic Z, Vucicevic K, Maric N, Kotur N,
Gasic V, Ugrin M, Stojiljkovic M, Dokmanovic L, Zukic B, Pavlovic S *Corresponding Author: Sonja Pavlovic, Ph.D., Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and
Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO BOX 23, 11010 Belgrade, Serbia.
Tel: +38111-3976445. Fax: +38111-3975808. E-mail: sonya@sezampro.rs page: 59 download article in pdf format
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Abstract
The UGT1A1 enzyme is involved in the metabolism of
bilirubin and numerous medications. Unconjugated hyperbilirubinemia,
commonly presented as Gilbert syndrome
(GS), is a result of decreased activity of the UGT1A1 enzyme,
variable number of TA repeats in the promoter of the
UGT1A1 gene affects enzyme activity. Seven and eight TA
repeats cause a decrease of UGT1A1 activity and risk GS
alleles, while six TA repeats contribute to normal UGT1A1
activity and non-risk GS allele. Also, the UGT1A1 (TA)n
promoter genotype is recognized as a clinically relevant
pharmacogenetic marker. The aim of this study was to assess
diagnostic value of UGT1A1 (TA)n promoter genotyping
in pediatric GS patients. Correlation of the UGT1A1 (TA)n
genotypes and level of unconjugated bilirubin at diagnosis
and after hypocaloric and phenobarbitone tests in these
patients was analyzed. Another aim of the study was to assess
pharmacogenetic potential of UGT1A1 (TA)n variants
in Serbia. Fifty-one pediatric GS patients and 100 healthy
individuals were genotyped using different methodologies,
polymerase chain reaction (PCR) followed by acrylamide
electrophoresis, fragment length analysis and/or DNA sequencing.
Concordance of the UGT1A1 (TA)n promoter
risk GS genotypes with GS was found in 80.0% of patients.
Therefore, UGT1A1 (TA)n promoter genotyping is not a
reliable genetic test for GS, but it is useful for differential
diagnosis of diseases associated with hyperbilirubinemia.
Level of bilirubin in pediatric GS patients at diagnosis was
UGT1A1 (TA)n promoter genotype-dependent. We found
that the frequency of pharmacogenetic relevant UGT1A1
(TA)n promoter genotypes was 63.0%, pointing out that
UGT1A1 (TA)n promoter genotyping could be recommended
for preemptive pharmacogenetic testing in Serbia.
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