胆红素尿苷二磷酸葡萄糖醛酸转移酶1A1基因突变与新生儿黄疸易感性的关系

Relationship between bilirubin uridine diphosphate-glucuronosyl transferase 1A1 gene mutation and susceptibility to neonatal jaundice

目的探讨胆红素尿苷二磷酸葡萄糖醛酸转移酶1A1基因(UGT1A1)第1外显子A1及启动子区TATA盒基因突变与广西新生儿黄疸的关系。方法 152例广西籍新生儿分为高胆红素血症组(病例组)102例及健康对照组50例,采用PCR和DNA直接测序法检测两组UGT1A1第1外显子及启动子区TATA盒基因型,比较两组UGT1A1 G71R基因型分布及等位基因频率差异,观察病例组UGT1A1基因突变类型及其不同基因型患儿出生后72 h后血清总胆红素水平。结果两组UGT1A1 G71R基因型分布及等位基因频率比较差异有统计学意义(P均<0.01)。病例组检出G71R错义突变40例,启动子A(TA)7突变2例,715C→T杂合无义突变1例。病例组G71R纯合子患儿血清总胆红素水平高于野生型及杂合子患儿(P均<0.05)。结论 UGT1A1基因G71R突变是广西新生儿黄疸主要突变类型,该突变与新生儿高胆红素血症有密切关系;新发现的715C→T无义突变可能是新生儿胆红素脑病发生的重要原因之一。

Objective To investigate the relationship between newborn jaundice of Guangxi population and the gene mutation in exon 1 and TATA box of bilirubin uridine diphosphate-glucuronosyl transferase （UGT1A1）.Methods Totally 102 cases with newborn hyperbilirubinemia （case group）and 50 neonates without newborn jaundice （control group）were included.TATA box and exon 1 genotypes of UGT1A1 in the two groups were detected by PCR and direct sequencing. UGT1A1 G71R genotype distribution and the differences in allele frequencies were compared between these two groups.The types of UGT1A1 mutation in the case group and the total serum bilirubin （TSB）levels in children patients at 72 hours af-ter birth with different genotypes were observed.Results Significant difference was found in the UGT1A1 G71R genotype distribution and allele frequencies between these two groups （all P 〈0.01）.There were 40 cases with G71R missense mu-tation,2 cases with （TA）7 insertion mutation,and 1 case with 715C→T heterozygous nonsense mutation in the case group.In the case group,the TSB level of G71R homozygous children patients was higher than that of the wild type and heterozygous children （all P 〈0.05）.Conclusions The G71R mutation of UGT1A1 gene is the main mutation type and closely related with newborn hyperbilirubinemia in Guangxi region.The new-found 715C→T nonsense mutation may be one of the important causes of neonatal bilirubin encephalopathy.