A Polymorphic Mutation, c.-3279T > G, in the UGT1A1 Promoter Is a Risk Factor for Neonatal Jaundice in the Malay Population

作者：Yusoff Surini; Takeuchi Atsuko; Ashi Chitose; Tsukada Masako; Ma'amor Nur H; Zilfalil Bin A; Yusoff Narazah M; Nakamura Tsutomu; Hirai Midori; Harahap Indra S K; Gunadi; Lee Myeong J; Nishimura Noriyuki; Takaoka Yutaka; Morikawa Satoru; Morioka Ichiro; Yokoyama Naoki; Matsuo Masafumi; Nishio Hisahide^*; van Rostenberghe Hans

来源：Pediatric Research, 2010, 67(4): 401-406.

DOI：10.1203/pdr.0b013e3181d22f78

The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glocuronidation. 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. (Pediatr Res 67: 401-406, 2010)

• 出版日期2010-4