A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.
The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the genotypes of c.-3279T>G, c.-3156G>A, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279T>G was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p = 0.003): the frequency of homozygosity for c.-3279G was much higher in patients than those in controls. Allele frequency of c.-3279G was significantly higher in patients than those in controls (p = 0.006). We then investigated changes in transcriptional activity because of c.-3279T>G. Luciferase reporter assay in HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was significantly lower than that of the c.-3279T allele in both the absence and presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that c.-3279T>G modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279T>G mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice.
Yusoff
Surini
S
Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Japan.
Takeuchi
Atsuko
A
Ashi
Chitose
C
Tsukada
Masako
M
Ma'amor
Nur H
NH
Zilfalil
Bin A
BA
Yusoff
Narazah M
NM
Nakamura
Tsutomu
T
Hirai
Midori
M
Harahap
Indra S K
IS
Gunadi
Lee
Myeong J
MJ
Nishimura
Noriyuki
N
Takaoka
Yutaka
Y
Morikawa
Satoru
S
Morioka
Ichiro
I
Yokoyama
Naoki
N
Matsuo
Masafumi
M
Nishio
Hisahide
H
van Rostenberghe
Hans
H
D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme