【作者】 于红；

【导师】 辛永宁；

【作者基本信息】 青岛大学 ， 内科学（消化内科）， 2018， 硕士

【摘要】 目的:通过对乙型肝炎肝硬化患者和健康对照者的临床资料分析及PNPLA3 I148M基因型检测,来评估PNPLA3 I148M基因多态性对乙型肝炎肝硬化患者的影响。方法:采用病例对照研究比较烟台市传染病医院肝病科病房住院的乙型肝炎肝硬化患者154例(观察组)与此期间在该院健康体检者150例(对照组)的临床资料和PNPLA3基因型多态性的差异,采用多聚酶链反应(PCR)法检测PNPLA3基因多态性,基因测序工作由博淼生物科技(北京)有限公司完成。结果:结果显示PNPLA3 I148M基因表型频率分布在对照组CC型占45.30%,GG型占30.00%,CG型占24.70%,观察组:CC型占31.17%,GG型占36.36%,CG型占32.47%;两组基因型分布差异有统计学意义(P<0.05)。而与CC纯合子携带者相比,携带危险等位基因G的CG、GG基因型者乙型肝炎肝硬化的发生风险增加(P<0.05,OR=1.914,95%CI为1.094~3.362;OR=1.763,95%CI为1.028~3.022)。观察组患者的生化指标明显高于对照组,有明显的统计学差异。其中两组的ALT相比,z=-9.241,P=0.000;两组的AST相比,z=-11.328,P=0.000;两组的TBIL相比,z=-11.332,P=0.000;两组的TG相比,z=-2.223,P=0.005;两组的CHOL相比,t=6.145,P=0.000;两组的GLU相比,t=-4.332,P=0.000。经Logistic回归分析发现对照组无论是性别、年龄,还是ALT、AST、TBIL、TG、CHOL、GLU水平均与PNPLA3 I148M基因多态性均未发现相关性(P>0.05)。观察组在性别、年龄、AST、TBIL、TG、GLU、WBC、PLT、HBe Ag、HBVDNA水平与PNPLA3基因型无相关性(P>0.05)。观察组患者PNPLA3 I148M基因型与谷丙转氨酶(ALT(P=0.050))、胆固醇(CHOL(P=0.032))、胆碱酯酶(CHE(P=0.048))、HBsAg滴度(P=0.002)、E值(FibroScan(P=0.010))有相关性,而且胆固醇是肝硬化的一个保护因素(P=0.032,OR=0.603,95%CI为0.308~0.959)。结论:PNPLA3 I148M基因多态性增加乙型肝炎肝硬化的发病风险,PNPLA3 I148M与乙型肝炎肝硬化的发生、发展具有相关性。更多还原

【Abstract】 Objective:To evaluate the effect of PNPLA3 I148 M gene polymorphism on hepatitis B cirrhosis,we analyzed and detected the I148 M genotype of PNPLA3 gene in hepatitis B cirrhosis group and healthy control group.Methods:The study included 154 hepatitis B cirrhosis patients with 150 healthy controls of Yantai infectious disease hospital.We investigated clinical data of them and examined genotypes of blood samples by polymerase chain reaction(PCR)and genotyping method.Results:Frequency distribution of hepatitis B liver cirrhosis group and comparison group PNPLA3 I148 M gene list type as follows: hepatitis B liver cirrhosis group CC type occupy 31.17%,GG type occupy 36.36%,CG type occupy 32.47%;the comparison group CC type occupy 30.00%,GG type occupy 24.70%,CG type occupy 24.70%.The difference of genetype distribution was statistically significant(P<0.05).Compare with CC homozygote carrier,CG and GG genotype carrying the G allele increased the risk of hepatitis B cirrhosis(P<0.05,OR=1.914,95%CI is 1.094~3.362;OR=1.763,95%CI is 1.028~3.022).There was significant difference in statistics between the hepatitis B cirrhosis group and comparison group(P<0.05).The biochemical indexes of patients with hepatitis B liver cirrhosis were significantly higher than those in the comparison group: ALT,z=-9.241,P=0.000;AST,z=-11.328,P=0.000;TBIL,z=-11.332,P=0.000;TG,t= z=-2.223,P=0.005;CHOL,t=6.145,P=0.000;GLU,t=-4.332,P=0.000.There was no correlation had been discovered in comparison group between PNPLA3 I148 M gene polymorphism and gender,age,glutamic-pyruvic transaminase cholesterol,glutamicoxalacetic transaminase,total bilirubin,triglyceride,blood sugar(P>0.05)through the logistic regression analysis.In the hepatitis B cirrhosis group,the logistic regression analysis showed that the PNPLA3 I148 M genotype was not associated with gender,age,glutamic-oxalacetic transaminase,total bilirubin,triglyceride,blood sugar,white blood cell,platelet,HBeAg titer or HBVDNA level(P>0.05).In the hepatitis B cirrhosis group,the logistic regression analysis showed that the PNPLA3 I148 M genotype was associated with glutamic-pyruvic transaminase(ALT(P= 0.050)),cholesterol(CHOL(P=0.032)),cholinesterase(CHE(P= 0.048)),HBsAg titer(P=0.002),and E value(FibroScan(P= 0.010))and that cholesterol is a protective factor about cirrhosis(P=0.032,OR=0.603,95%CI 0.308~0.959).Conclusions:Polymorphisms in the PNPLA3 gene may play an important role in mediating susceptibility to developing hepatitis B liver cirrhosis in the Chinese population.The rs738409 polymorphism,in particular,is related to development and progression of hepatitis B liver cirrhosis and may play a role in increasing the risk of hepatitis B cirrhosis.更多还原