维吾尔族新生儿高未结合胆红素血症UGT1A1基因突变分析

Analysis of UGT1A1 gene mutation in Uygur neonates with unconjugated hyperbilirubinemia

目的研究维吾尔族高未结合胆红素血症新生儿的尿苷二磷酸葡萄糖醛酸转移酶1A1(uridine diphosphate glucuronosyltransterase 1A1,UGT1A1)基因突变情况。方法选取2013—2016年新疆维吾尔自治区人民医院住院治疗的34例高未结合胆红素血症患儿为试验组,选取同期11例生理性黄疸患儿为对照组。提取外周血基因组DNA,扩增UGT1A1基因的编码序列及启动子区,对扩增产物进行测序确定基因突变。结果病例资料中发生UGT1A1基因突变共7种,分别为第1外显子Gly71Arg(G71R),Val674Gly(V225G),第3外显子Pro1091Leu(P364L),Asp1195Asn(D399N),第5外显子Pro1352Leu(P451L),Tyr486Asp(Y486D),TATAA盒TA插入转录突变。其中G71R及TATAA盒TA插入转录突变发生频率最高,但试验组及对照组突变频率差异无统计学意义(χ~2=1.681,P=0.195;χ~2=0.214,P=0.643);在维吾尔族与汉族对照组中G71R突变频率差异无统计学意义(χ~2=0.253,P=0.615),TATAA盒TA插入转录突变频率差异有统计学意义(χ~2=4.675,P=0.031)。结论新疆维吾尔族新生儿中UGT1A1基因突变存在多种类型;TATAA盒TA插入转录突变频率均明显高于当地汉族新生儿。

Objective To analyze the mutation of uridine diphosphate glucuronosyltransterase 1 A1,UGT1 A1 gene in Uygur neonates with unconjugated hyperbilirubinemia. Methods Select the neonates with unconjugated hyperbilirubinemia in People＇s Hospital of Xinjiang Uygur Autonomous Region during 2013-2016. The genomic DNA of peripheral blood was extracted. Amplify the coding sequence and promoter region of UGT1 A1 gene,which were sequenced to identify gene mutations.A total 34 cases were enrolled as hyperbilirubinemia group and 11 cases of physiological jaundice were selected as control group. Results Seven mutations were detected,and they were 71 Arg（G71 R）,Val674 Gly（V225 G）at exon 1,Pro1091 Leu（P364 L）,Asp1195 Asn（D399 N）at exon 3,Pro1352 Leu（P451 L）,Tyr486 Asp（Y486 D）at exon 5,respectively. TATAA cassette had transcription mutation of insertion TA. The highest mutation frequency occurred in G71 R and insertion TA into TATAA cassette. However,there was no statistical difference in frequency of mutation between the hyperbilirubinemia group and the control group（χ~2=1.681,P=0.195;χ~2=0.214,P=0.643）;there was no statistical difference in G71 R mutation frequency between Han and Uygur control group（χ~2=0.253,P=0.615）,but there was statistically significant difference in insertion TA into TATAA cassette between Han and Uygur group（χ~2=4.675,P=0.031）. Conclusion There are several types of mutations detected in Xinjiang Uygur newborns,and Uygur neonates have a significantly higher mutation frequency ofTA into TATAA cassette than the local Han Chinese newborns.