中文摘要：

目的：通过对编码肝内与胆汁生成及分泌相关转运蛋白基因的序列分析．辅助诊断l临床确诊困难的药物性胆汁淤积。方法：常规检测1例反复肝功能异常、黄疸患者的肝功能、血清胆红素水平及病毒性肝炎、代谢性肝病和自身免疫性肝病的相关指标．以排除相关肝病；并进行肝组织活检病理学检查，对编码肝内转运蛋白相关基因ABCBll、ABCB4和ATP881的外显子及剪接位点进行序列分析．排除家族性肝内胆汁淤积；再检测其药物性胆汁淤积相关易感基因变异位点。结果：血清谷氨酸氨基转移酶轻度异常．总胆红素227．6μmol／L，直接胆红素／间接胆红素比值为1．55：肝组织病理学检查提示为药物性胆汁淤积，但不能排除家族性肝内胆汁淤积：基因序列分析发现，ABCBll基因上的c．1331T〉C，p．Val444A1a纯合变异（rs2287622），是药物性胆汁淤积患病的易感基因变异位点。结论：对肝内与胆汁生成及分泌相关转运蛋白基因进行DNA序列分析．有助于药物性胆汁淤积的确诊和鉴别。

英文摘要：

Objective To evaluate the use of sequence analysis of hepatic transporter genes as an adjuvant for diagnosis of drug-induced cholestasis. Methods Liver function test, bilirubin level, and serology markers for viral hepatitis, metabolic and autoimmune liver diseases were tested in a patient with recurrent liver function abnormality and jaundice for ruling out related liver diseases, and liver biopsy specimen was taken for histological examination, and genomic DNA was extracted from blood leukocytes for polymerase chain reaction （PCR） amplification of whole exons and splicing-sites in ABCBll, ABCB4 and ATP8B1 genes followed by direct sequencing to find out the mutations or polymorphisms associated with familial cholestasis and drug-induced cholestasis. Results Serum tests showed mild elevated transaminases and obviously increased bilirubin （TBil 227.6 μmol/L, DBil/IBiI=l.55）. Viral hepatitis, metabolic and autoimmune liver diseases were ruled out. Histologic analysis of liver biopsy specimen suggested drug-induced hepatitis and suspicious familial cholestasis. Gene sequencing results had not found correlated mutations for familial cholestasis but a single nucleotide polymorphism （SNP） c. 1331 T〉C, p.Va1444Ala （rs2287622） in exon 12 of ABCB 11 gene was found, which is associated with decreased hepatic BSEP expression and is a risk factor for drug-induced cholestasis. Conclusions Sequence analysis of hepatic transporter gene could play an adjuvant role in the definitive and differential diagnosis of drug-induced cholestasis.