SCREENING OF UGT1A1 GENE AND GENOTYPE-PHENOTYPE CORRELATIONSHIP IN NEONATAL JAUNDICE FROM A SAMPLE OF NEWBORNS IN KELANTAN
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Date
2012-04
Authors
NUR HASNAH, MA’AMOR
Journal Title
Journal ISSN
Volume Title
Publisher
Pusat Pengajian Sains Perubatan Universiti Sains Malaysia
Abstract
The rate limiting step of bilirubin excretion is the glucuronidation of bilirubin in the
liver, a process that is catalyzed by an enzyme, Uridine glucuronyl transferase. This
enzyme is encoded by the UGT1A1 gene. In several populations, mutations in this
gene have been shown to cause neonatal jaundice. However data on the Malaysian
Malay population are scanty at best. The objectives of this study included: to
determine the frequency of variants in the exons of the UGT1A1 gene in a
population of term Malay neonates with jaundice and without jaundice, and to
correlate the genotype finding with some phenotypic data. A cross sectional study
was performed in Kelantan, Malaysia. A group of term jaundiced neonate (jaundice
group) and a group of term non-jaundiced neonate (control group) were included in
the study. Blood was taken for genetic testing. DNA was extracted from blood
before polymerase chain reaction (PCR) was performed. Denaturing high
performance liquid chromatography (DHPLC) was performed to screen the whole
exons in the UGT1A1 gene and for subjects that were identified to have a
heteroduplex peak in DHPLC, sequencing was performed to confirm the mutation or
SNP. Clinical data were collected as part of a larger study. Data were entered in
SPSS and analyzed. Two hundred and eighteen six (286) neonates were included in
each the jaundice and control groups. Nine variants have been identified in this
study. The most common variant was the G71R variant in exon 1, which is common
in other Asian populations as well. Only 4 of the other variants detected in this study
had been reported as SNPs in another population. Other variants appeared to be
novel mutations. Even though variants were found in a higher number in the
jaundice group than in the control group, the difference between the groups was
statistically not significant. There were also no significant differences in severity of
neonatal jaundice and in haemolysis between jaundiced neonates with and without
identified variants in the UGT1A1 gene. The G71R variant had been identified as the
most common variant in the exons of the UGT1A1 gene. The results of this study did
not clearly show that this was a risk factor for neonatal jaundice.
Description
Keywords
Paediatrics