Gilbert综合征合并病毒性肝炎的基因突变模式及其与临床资料的关系探索  

Gene mutation pattern of Gilbert’s syndrome combined with viral hepatitis and its relationship with the exploration of clinical data

作　　者：宁会彬 靳慧鸣 刘翠平 彭真 李宽 肖二辉 尚佳 Ning Huibin;Jin Huiming;Liu Cuiping;Peng Zhen;Li Kuan;Xiao Erhui;Shang Jia(Henan Provincial People's Hospital,Zhengzhou University People's Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院郑州大学人民医院,郑州450003

出　　处：《中华肝脏病杂志》2020年第10期855-860,共6页Chinese Journal of Hepatology

基　　金：河南省医学科技攻关项目(201503171)。

摘　　要：目的研究Gilbert综合征(GS)是否合并病毒性肝炎时其基因突变情况及其与相关临床资料的关系。方法回顾性分析2013年8月至2018年12月于河南省人民医院感染科收治的GS患者资料,包括合并病毒性肝炎的患者,分析其基因突变的模式与一般资料(年龄、性别等)、肝脏生物化学指标的关系,并分析是否合并病毒性肝炎情况下上述资料的差异。计量资料比较采用t检验,分类资料比较采用χ2检验,非正态分布的资料采用中位数和四分位间距表示集中和离散趋势。用秩和检验比较组间差异。结果共收集符合条件的107例GS患者资料,男女比例为4.94∶1(89∶18),发病年龄(36.36±12.51)岁。除丙氨酸转氨酶和总胆红素为正常或轻度升高外,天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶均在正常值范围。合并病毒性肝炎组49例(36例合并HBV、13例合并HCV),单纯GS组58例。两组患者总胆红素水平单纯GS组高于合并病毒性肝炎组(Z=0.035,P<0.05),在性别、年龄、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶数据间差异均无统计学意义(P值均>0.05)。107例患者均进行了GS特异性编码的尿苷二磷酸葡糖苷酸转移酶UGT1A1基因检测,突变主要发生在启动子上游PBREM-3263(-3279)(86例)和启动子TATA盒TA插入突变(71例),以及编码区外显子EXON1上的GGA-AGA Gly71Arg(57例)突变,突变形式均可表现纯合及杂合异常。基因检测数据中发生的主要突变形式组合发生率依次为A2+B2+C2(17例,25.23%)、A1+B1(17例,15.89%)、A2(11例,10.28%)、C2(10例,9.34%)、A2+B2(7例,6.54%)、A1+B2(7例,6.54%)、C1(7例,6.54%),不同突变组合在是否合并肝炎患者间差异均无统计学意义(P值均>0.05)。总数据分析结果显示单一位点突变组总胆红素水平高于多点突变组(Z=2.019,P=0.043),其他生物化学指标无影响(P值均>0.05,差异均无统计学意义)。进一步分析结果显示单�Objective To study whether gene mutation pattern of Gilbert’s syndrome(GS)is combined with viral hepatitis and its relationship with relevant clinical data.Methods Clinical data of GS patients combined with viral hepatitis who was admitted to the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2013 to December 2018 was retrospectively analyzed.The relationship between gene mutation pattern,general data(age,gender,etc.)and liver biochemical indexes was analyzed.The differences of the above data in patients with or without combined viral hepatitis were analyzed.The measurement data were compared by t-test.The categorical data was compared by theχ2 test.The median and interquartile range of non-normally distributed data was used to indicate the central and discrete tendency.Results A total of 107 GS eligible cases data were collected.The male to female ratio was 4.94:1(89:18).The average age of onset was(36.36±12.51)years.Alanine aminotransferase and total bilirubin levels were normal or slightly elevated,while aspartate aminotransferase,alkaline phosphatase,andγ-glutamyltransferase were all within the normal range.There were 49 cases in the combined viral hepatitis group(36 cases with HBV and 13 cases with HCV),and 58 cases in the GS alone group.Total bilirubin level in GS alone group was higher than the combined viral hepatitis group(z=0.035,P<0.05),and there were no statistically significant differences in gender,age,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and gamma glutamyltransferase(P>0.05).Uridine diphosphate glucuronide transferase 1A1(UGT1A1),specifically encoded by GS was detected in all 107 cases.Mutations was mainly occurred in the upstream promoter PBREM-3263(-3279)(86 cases)and TATA box TA insertion mutation(71 cases),and GGA-AGA Gly71Arg(57 cases)mutation in EXON1 of the coding region.All mutation forms had manifestations of homozygous and heterozygous abnormalities.The combined incidence of main mutation forms in the genetic te

关 键 词：河南省人民医院 尿苷二磷酸葡萄糖醛酸转移酶 丙氨酸转氨酶 发病年龄 病毒性肝炎 天冬氨酸转氨酶 基因突变 多点突变 

分 类 号：R575[医药卫生—消化系统]