胆红素-尿苷二磷酸葡萄糖醛酸基转移酶G71R基因型对广西地区新生儿黄疸程度的影响

Roles of UGT 1A1 gene mutation in the development of neonatal hyperbilirubinemia in Guangxi

目的 探讨胆红素-尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT 1A1）基因突变对广西新生儿黄疸的影响.方法 收集73例高胆红素血症新生儿及31例健康新生儿外周血,应用突变特异性扩增系统（amplification refractory mutation system,ARMS）法及直接测序法对所有新生儿行UGT1A1基因G71R突变检测,分析胆红素脑病发生率,胆红素峰值及总胆红素（total serum bilirubin,TSB）〉20 mg/dl的机会比.结果 （1）本研究人群G71R等位基因频率为0.1915,病例组为0.2329,健康对照组为0.097,病例组的G71R等位基因频率显著高于健康对照组（P〈0.05）.（2）G71R纯合子的胆红素脑病发病率及72 h的TSB浓度（28.57%,23.12±4.58 mg/dl）均高于野生型组（0%,17.68±2.69 mg/dl）,差异有统计学意义（P〈0.001）.（3）G71R纯合子组中5例的TSB〉20 mg/dl,G71R纯合子TSB〉20 mg/dl的机会比（odds ratio,OR）为7.955,总体机会比95%可信区间（confidence interval,CI）为（1.349,46.899）.结论 G71R突变与本地新生儿黄疸的发病存在相关性.G71R纯合子的胆红素脑病发病率及生后72 h的TSB较对照组及野生型增高.G71R纯合子发生TSB〉20 mg/dl的危险性是野生型的7.955倍.

Objective Neonatal unconjugated hyperbilirubinemia is one of the most common conditions encountered by the practicing pediatricians.Although it is usually self-limited and benign,the condition is of importance because of the rare instances in which severe hyperbilirubinemia can lead to bilirubin encephalopathy or kernicterus.The uridine diphosphate-glucuronosyl transferase 1A1（UGT 1A1）gene controls bilirubin conjugation by determining the structure of the enzyme glucuronosyltransferase,which is synthesized in the hepatocyte.In the recent years much has been learned about the relationship between UGT 1A1 gene mutation and neonatal hyperbilirubinemia.This study aimed to investigate the roles of UGT 1A1 gene mutation in the development of neonatal hyperbilirubinemia in Guangxi.Methods A total of 73 cases with hyperbilirubi nemia and 31 healthy neonates were enrolled.UGT 1A1 G71R genotypes were identified by the（amplification refractory mutation system,ARMS）and direct sequencing method in all the neonates.To analyze the incidence of bilirubin encephalopathy,the peak（total serum bilirubin,TSB）concentration after 72 hours of age,and the possibility of TSB 〉 20 mg/dl of each group.Results（1）The frequencies of allele G71R were 0.1915 in this study,0.2329 in hyperbilirubinemia group vs.0.097 in healthy groups.The allele gene frequency of G71R in neonatal hyperbilirubinemia was higher than that in the normal group（P 〈0.05）.（2）Homozygous neonates had higher possibility to develop bilirubin encephalopathy and higher TSB concentration 72 hours after birth（28.57% ,23.12 ±4.58）than the normal group（0%,17.68±2.69）.The difference between the former two was significant（P 〈0.001）.（3）The TSB of the 5 neonates was 〉 20 mg/dl in G71R homozygous type,the odds ratio and 95% CI were 7.955（1.349,46.899）.Conclusion（1）G71R mutation gene was associated with neonatal jaundice in Guangxi region.（2）The possibility of TSB 〉 20 mg/dl in G71R homozygous was higher than those of the wild-type.（3）The incidence of bilirubin encephalopathy and TSB concentration after 72 hours of age for neonates who were homozygous to G71R gene were higher than the wild-type.