NOD2及MCP-1基因SNP与乙肝肝硬化自发性腹膜炎的相关研究

发布时间：2018-03-07 04:15

  本文选题：乙肝肝硬化　切入点：自发性腹膜炎　出处：《遵义医学院》2017年硕士论文　论文类型：学位论文

【摘要】：目的:自发性细菌性腹膜炎(Spontaneous bacterial peritonitis,SBP)是严重威胁生命的乙肝肝硬化并发症,尽管乙肝肝硬化SBP的治疗方案不断完善,院内死亡率仍达到10%-50%。本文旨在探究核苷酸结合寡聚化结构域蛋白2(Nucleotide-binding oligomerization domain-containing protein 2,NOD2)基因单核苷酸多态性(Single nucleotide polymorphism,SNP)(R702W,G908R,P268S)及单核细胞趋化蛋白-1(Monocyte chemotactic protein-1,MCP-1)基因SNP(A2518G)与乙肝肝硬化SBP易感性的相关关系,以及血清白蛋白(Albumin,ALB)、总胆红素(Total bilirubin,TBIL)、肝功能分级、血清钠、降钙素原(Procalcitonin,PCT)与乙肝肝硬化SBP发生、发展的关系,对乙肝肝硬化腹水并发SBP进行早期病情判断、评估预后及干预治疗,从而提高生存率有重要意义。方法:选取2015年1月至2016年6月于大连市第六人民医院住院的80例乙肝肝硬化腹水患者,其中40例并发自发性腹膜炎(SBP组)、40例无自发性腹膜炎(非SBP组)和30例门诊体检人群作为健康对照组。采集治疗前病例组外周静脉血及腹水、对照组的外周静脉血,提取全血基因组DNA、PCR扩增目的基因、限制性内切酶酶切PCR产物、琼脂糖凝胶电泳,获得NOD2基因的3个SNP(R702W,G908R,P268S)及MCP-1启动子(A-2518G)基因SNP的基因型。同时收集临床资料,统计分析探讨NOD2及MCP-1的基因SNP以及血清ALB、TBIL、肝功能分级、血清钠、PCT与乙肝肝硬化腹水并发SBP的关系。结果:通过PCR技术得到NOD2基因(R702W,G908R,P268S)三种扩增产物,酶切后病例组及对照组G908R、P268S未观察到突变基因型;R702W仅2例(2/40,0.05%)SBP组观察到突变型但非SBP组及对照组未观察到突变型。MCP-1(A-2518G)观察到三种基因型:SBP组基因型AG明显高于健康对照组(χ2=10.95,P=0.004);非SBP组GG基因型频率大于健康对照组(χ2=24.78,P0.001);AG基因型SBP组明显高于非SBP组,P0.05;非SBP组基因型GG高于SBP组,P0.05;等位基因比较:等位基因A在SBP组明显高于非SBP组,P0.05;等位基因G在非SBP组明显高于SBP组,P0.05;等位基因G在SBP组及非SBP组的分布频率均大于健康对照组18例(30.0%),P0.05,差异均具有统计学意义。两组间的临床指标比较结果提示:血清ALB、TBIL、肝功能分级,血清钠、PCT差异具有统计学意义,P0.05。性别、年龄、凝血酶原时间(Prothrombin time,PT)、丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(Aaspartate aminotransferase,AST)两组间没有统计学意义。结论:1.NOD2二种SNP(G908R,P268S)基因型在汉族人群80例乙肝肝硬化患者及30例对照组中未观察到突变型,虽然SBP组有2例(2/40,0.05%)R702W突变SNP但没有统计学意义,提示NOD2三种SNP(G908R、P268S、R702W)基因型可能均不是所研究汉族人群乙肝肝硬化腹水并发SBP的易感基因型,而MCP-1(A2518G)AG基因型和A等位基因可能增加汉族人群乙肝肝硬化腹水并发SBP的发生率,对携带AG基因型及A等位基因乙肝肝硬化腹水患者临床综合评估后可以考虑尽早进行治疗。2.血清ALB、TBIL、血清钠、PCT、Child-Pugh分级C级均为乙肝肝硬化自发性腹膜炎发生的影响因素。
[Abstract]:Objective: spontaneous bacterial peritonitis (Spontaneous bacterial, peritonitis, SBP) is a serious threat to the life of the complications of liver cirrhosis, although the treatment of hepatitis B cirrhosis SBP continues to improve, the in-hospital mortality rate still reached 10%-50%. this paper aims to explore the nucleotide binding oligomerization domain protein 2 (Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene polymorphism Single nucleotide polymorphism (SNP), R702W, G908R, P268S) and monocyte chemoattractant protein -1 (Monocyte chemotactic protein-1, MCP-1) SNP (A2518G) gene associated with SBP susceptibility to hepatitis B cirrhosis, and serum albumin (Albumin, ALB), total bilirubin (Total, bilirubin, TBIL), the grade of liver function. Serum sodium, procalcitonin (Procalcitonin, PCT) and hepatitis B cirrhosis SBP, the development of relations of hepatitis B cirrhosis complicated with SBP Early diagnosis, prognosis and therapeutic intervention, so as to improve the survival rate has important significance. Methods: 80 cases of liver cirrhosis and ascites were selected from January 2015 to June 2016 in the Sixth People's Hospital of Dalian, of which 40 cases of spontaneous bacterial peritonitis (SBP group), 40 cases of spontaneous bacterial peritonitis (non SBP group) and 30 cases of outpatients as healthy control group. The treatment group were collected before the peripheral venous blood and ascites, control peripheral blood group, genomic DNA extraction, PCR amplification of the target gene, restriction endonuclease PCR, agarose gel electrophoresis, 3 SNP NOD2 genes (R702W, G908R, P268S) and MCP-1 (A-2518G) gene promoter SNP gene. At the same time to collect clinical data, statistical analysis of the SNP gene of NOD2 and MCP-1 and serum ALB, TBIL, liver function, serum sodium, PCT and hepatitis B patients with liver cirrhosis SBP鐨勫叧绯，

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