Frequencies of A(TA)7TAA, G71R, and G493R mutations of the UGT1A1 gene in the Malaysian population.
BACKGROUND
Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice.


OBJECTIVE
The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls.


METHODS
The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography.


RESULTS
Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p=0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p=0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p=0.476).


CONCLUSIONS
The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population.
Yusoff
Surini
S
Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia.
Van Rostenberghe
Hans
H
Yusoff
Narazah M
NM
Talib
Norlelawati A
NA
Ramli
Noraida
N
Ismail
N Zainal A N
NZ
Ismail
W Pauzi W
WP
Matsuo
Masafumi
M
Nishio
Hisahide
H
D002851:Chromatography, High Pressure Liquid; D005787:Gene Frequency; D005878:Gilbert Disease / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics; D007231:Infant, Newborn; D008296:Malaysia / Q000453:epidemiology; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme