家族性胆红素异常患者UGT1A1基因检测及其基因多态性分析  

The polymorphism of UGT1A1 gene in patients with Gilbert's syndrome

作　　者：孙梅[1] 谈国蕾[1] 王建芳[1] 吴旭平[1] 

机构地区：[1]东南大学附属第二医院肝病研究室,南京210003

出　　处：《肝脏》2017年第1期15-19,共5页Chinese Hepatology

基　　金：南京市医学科技发展资金资助项目(YKK13151,QRX11236)

摘　　要：目的了解家族性胆红素异常患者和正常人尿苷二磷酸葡萄糖醛酸转移酶1A1基因(UGT1A1)的变异情况。方法分别检测29例家族性胆红素异常患者和22例正常人群的UGT1A1,比较分析其多态性分布。分别设计UGT1A1基因各个外显子及增强子区扩增引物,对PCR扩增产物进行测序。结果主要检测到UGT1A1基因中三个区域的变异,增强子区,外显子1和TATA盒区的变异。其中29例Gilbert综合征患者中,增强子区UGT1A1*603279(T>G),10例G/G变异,15例T/G杂合;TATA盒区,15例TATA(7)变异,2例TATA(6)/TATA(7)杂合;外显子1中,UGT1A1*6211(G>A),3例A/A纯合变异,15例G/A杂合变异;UGT1A1*27686(C>A),3例A/C杂合变异。20例正常对照组中,增强子区UGT1A1*60 3279(T>G),2例G/G变异,11例T/G杂合;TATA盒区,7例TATA(6)/TATA(7)杂合;外显子1中,UGT1A1*6211(G>A),5例G/A杂合变异;UGT1A1*27686(C>A),无A/C杂合变异。结论家族性胆红素异常患者中UGT1A1变异率高于正常对照组,UGT1A1变异可作为Gilbert综合征诊断的参考指标。Objective To investigate the polymorphism of UDP glucuronosyltransferase family 1 member Al （UGTl Al） in 29 patients with Gilberts syndrome and 22 healthy controls. Methods DNA isolated from peripheral blood and amplified by polymerase chain reaction （PCR） was subjected for sequencing UGTlAl gene exons and enhancer regions. Results UGTlAl gene variations were detected in enhancer region, TATA box region and the exon 1 region, respectively. Among 29 patients with Gilbert＇s syndrome, 10 G/G homozygosis and 15 T/G heterozygosis were detected in enhancer region UGT1A1＊60 3729（T〉G） ,15 TATA（ 7） TAA homozygosis and 2TATA（ 6）/TATA（ 7） TAA heterozygosis in TATA box region, and 3 A/A homozygosis and 15 G/A heterozygosis in exon 1 region. In 20 healthy controls, 2 G/G and 11 T/G mutations were detected in enhancer region UGTlAl ＊ 60 3729（T〉G）, 7 homozygous TATA（6）/TATA（7）TAA mutation in TATA box region, and 5 G/A mutations in exon 1 region. Conclusion UGTlAl gene mutations in patients with Gilberts syndrome is higher than that in healthy controls, which could only be used as a reference index for diagnosis of Gilberts syndrome.

关 键 词：尿苷二磷酸葡萄糖醛酸转移酶1A1基因 GILBERT综合征 基因多态性 

分 类 号：R575[医药卫生—消化系统]