title: A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.
abstract: 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.
authors.affiliation: Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Japan.
authors.forename: Surini
authors.initials: S
authors.lastname: Yusoff
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Chitose
authors.initials: C
authors.lastname: Ashi
authors.forename: Masako
authors.initials: M
authors.lastname: Tsukada
authors.forename: Nur H
authors.initials: NH
authors.lastname: Ma'amor
authors.forename: Bin A
authors.initials: BA
authors.lastname: Zilfalil
authors.forename: Narazah M
authors.initials: NM
authors.lastname: Yusoff
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.forename: Indra S K
authors.initials: IS
authors.lastname: Harahap
authors.lastname: Gunadi
authors.forename: Myeong J
authors.initials: MJ
authors.lastname: Lee
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishimura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takaoka
authors.forename: Satoru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Morioka
authors.forename: Naoki
authors.initials: N
authors.lastname: Yokoyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Hisahide
authors.initials: H
authors.lastname: Nishio
authors.forename: Hans
authors.initials: H
authors.lastname: van Rostenberghe
mesh_terms: 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
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme