云南地区53例先天性高胆红素血症临床特征及UGT1A1基因多态性分析  

Clinical Characteristics and Polymorphism of UGT1A1 Gene in 53 Cases of Congenital Hyperbilirubinemia in Yunnan

作　　者：李娟[1] 邓成俊[1] 何舒丽 李英 王美芬[2] LI Juan;DENG Chengjun;HE Shuli;LI Ying;WANG Meifen(Dept.of Gastroenterology,Kunming Children’s Hospital,Kunming Yunnan 650034,China;Dept.of Infection,Kunming Children’s Hospital,Kunming Yunnan 650034,China)

机构地区：[1]昆明市儿童医院消化内科,云南昆明650034 [2]昆明市儿童医院感染一科,云南昆明650034

出　　处：《昆明医科大学学报》2024年第5期136-143,共8页Journal of Kunming Medical University

基　　金：昆明市卫生健康委员会卫生科研基金资助项目(2022-06-01-007)。

摘　　要：目的探讨云南地区53例UGT1A1基因突变所致的先天性高胆红素血症(Gilbert综合征、Crigler-Najjar综合征)的临床特征及UGT1A1基因突变特点。方法选取2017年1月至2022年12月间昆明市儿童医院消化内科53例Gilbert综合征(GS组)、Crigler-NajjarⅡ型综合征(CN-2组)患儿的临床数据、UGT1A1基因突变结果,回顾性分析患儿的临床特征、实验室检查结果和基因多态性。结果少数民族患儿均在2组中发病率较高,CN-2组中女性比例比GS高。肝脏系统方面,CN-2组TBil、IDB水平较GS组更高,差异均有统计学意义(P<0.05),GS组肝脏结构正常,CN-2组有3例患者肝胆结构有异常。肝外系统方面,血液系统、糖代谢无异常,血脂、甲状腺功能代谢有异常,GS组有维生素D不足,CN-2组存在维生素A、D缺乏及维生素E水平下降。2组患儿均存在心脏结构异常,但CN-2组较GS组发病率高。在所有患者中,突变频率最高的为发生在5号外显子上的c.1456T>G(32例,60.37%),其次为c.1091C>T(14例,26.42%)、1号外显子c.211G>A(6例,11.32%)和c.1198A>C(4例,7.55%)。c.1456T>G位点突变在GS组和CN-2组的频率分别为69.23%和57.5%(9例和23例),2组间差异无统计学意义(P>0.05)。2组中,其次突变频率较高的为c.1091C>T(4例和10例),2组间差异无统计学意义(P>0.05)。UGT1A1基因单倍型1、3、4在GS组和CN-2组间的频率差异均有统计学意义(P<0.05)。UGT1A1基因的4种主要突变形式,在性别和不同民族间,差异无统计学意义(P>0.05)。结论GS组和CN-2组在肝脏系统、肝外系统的临床表现存在不同,UGT1A1基因突变频率最高的为发生在5号外显子上的c.1456T>G。Objective To investigate the clinical characteristics of 53 cases of congenital hyperbilirubinemia(Gilbert syndrome,Crigler-Najjar syndrome)caused by UGT1A1 gene mutation in Yunnan Province and the characteristics of UGT1A1 gene mutation.Methods 53 cases were selected from the Department of Gastroenterology of Kunming Children’s Hospital from January 2017 to December 2022 and divided into Gilbert syndrome(GS)group and Crigler-Najjar-2(GN-2)group.The clinical data and genetic test results of children with type I1 syndrome(CN-2 group)and the clinical manifestations,laboratory test results and gene polymorphisms of the children were retrospectively analyzed.Results Children from the ethnic minority had the higher incidence in both groups.The proportion of females in CN-2 group was higher than that in GS group.In terms of liver system,the levels of TBil and IDB in CN-2 group were higher than those in GS group,with statistical significance(all P values<0.05).The liver structure in GS group was normal,while 3 patients in CN-2 group had the abnormal liver and biliary structure.In the extra-hepatic system,there were no abnormalities in blood system and glucose metabolism,abnormal blood lipids and thyroid function metabolism,vitamin D deficiency in GS group,vitamin A and D deficiency and vitamin E decreased in CN-2group.There were cardiac structural abnormalities in both groups,but the incidence of CN-2 group was higher than that of GS group.Among all the patients,the mutation frequency of c.1456T>G in exon 5 was the highest(32 cases,60.37%),followed by c.1091C>T(14 cases,60.37%).Exon 1,C.211g>A(6 cases,11.32%),and C.1198a>C(4 cases,7.55%).The frequency of c.1456T>G mutation in GS group and CN-2 group was 69.23%and 57.5%(9 and 23 cases),respectively,and there was no significant difference between the two groups(P>0.05).Among the two groups,the second most frequent mutation was c.1091C>T(4 cases and 10 cases),and there was no statistical significance between the two groups(P>0.05).The frequencies of UGT1A1 haplotypes 1�

关 键 词：GILBERT综合征 Crigler-Najjar综合征 血清总胆红素 UGT1A1 基因型 

分 类 号：R72[医药卫生—儿科]