胆红素代谢关键酶的编码基因UGT1A1基因多态是新生儿黄疸高发的重要遗传因素。我们前期的研究提示着UGT1A1基因启动子区TATA盒（UGT1A1*28）的变异与新生儿黄疸的临床表现并不一致，不同种族人群的研究结果存在很大的差异，具体机制不明。我们推测表观遗传学修饰可能是背后的机制。本课题拟以UGT1A1启动子多态为切入点，从基因多态和表观遗传学两个角度对新生儿黄疸发病的分子机制进行探讨：首先，病例-对照研究，探寻UGT1A1启动子区UGT1A1*28的变异和CpG岛甲基化与新生儿黄疸易感性的关联；其次，研究不同种族新生儿UGT1A1启动子多态的分布、CPG甲基化、转录因子水平及新生儿黄疸的发生率差异，明确该差异在人群新生儿黄疸易感性中所发挥的作用。最后，细胞水平研究UGT1A1启动子甲基化修饰在新生儿黄疸发生中的作用及机制。为阐明新生儿黄疸易感性的种族差异及个体化治疗提供理论依据。

UGT1A1 variation, including promoter TATA box variation and coding region 211 G to A (Gly71Arg) variation, has been shown to be associated with an increased incidence and severity of neonatal hyperbilirubinemia. However, our previous study has found that there were more heterozygotes of the (TA)7 repeat variant in the control group.The promoter TATA box variation in the UGT1A1 gene seem to may not contribute, and may even have a protective effect to neonatal hyperbilirubinemia in Asian population.This finding is in contrast to previous reports in Caucasian population. The contradicted role of (TA)7 repeat variant in neonatal hyperbilirubiemia merit further study. The aim of the present study is to firgure our the following scientific issues. Firstly,we will to define the effect of promoter TATA box variation in neonatal hyperbilirubinemia susceptibility . Secondly, we will investigate the features of methylation in the promoter region of UGT1A1 gene and the association between gene promoter methylation and neonatal hyperbilirubilinemia. At last, we will explore the possible mechanism of DNA methylation and neonatal hyperbilirubiem .This will lay a foundation for develop new drug in use of lowing TSB level in neonatal with severe hyperbilirubinemia。