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NOD2及MCP-1基因SNP與乙肝肝硬化自發(fā)性腹膜炎的相關(guān)研究

發(fā)布時間:2018-03-07 04:15

  本文選題:乙肝肝硬化 切入點(diǎn):自發(fā)性腹膜炎 出處:《遵義醫(yī)學(xué)院》2017年碩士論文 論文類型:學(xué)位論文


【摘要】:目的:自發(fā)性細(xì)菌性腹膜炎(Spontaneous bacterial peritonitis,SBP)是嚴(yán)重威脅生命的乙肝肝硬化并發(fā)癥,盡管乙肝肝硬化SBP的治療方案不斷完善,院內(nèi)死亡率仍達(dá)到10%-50%。本文旨在探究核苷酸結(jié)合寡聚化結(jié)構(gòu)域蛋白2(Nucleotide-binding oligomerization domain-containing protein 2,NOD2)基因單核苷酸多態(tài)性(Single nucleotide polymorphism,SNP)(R702W,G908R,P268S)及單核細(xì)胞趨化蛋白-1(Monocyte chemotactic protein-1,MCP-1)基因SNP(A2518G)與乙肝肝硬化SBP易感性的相關(guān)關(guān)系,以及血清白蛋白(Albumin,ALB)、總膽紅素(Total bilirubin,TBIL)、肝功能分級、血清鈉、降鈣素原(Procalcitonin,PCT)與乙肝肝硬化SBP發(fā)生、發(fā)展的關(guān)系,對乙肝肝硬化腹水并發(fā)SBP進(jìn)行早期病情判斷、評估預(yù)后及干預(yù)治療,從而提高生存率有重要意義。方法:選取2015年1月至2016年6月于大連市第六人民醫(yī)院住院的80例乙肝肝硬化腹水患者,其中40例并發(fā)自發(fā)性腹膜炎(SBP組)、40例無自發(fā)性腹膜炎(非SBP組)和30例門診體檢人群作為健康對照組。采集治療前病例組外周靜脈血及腹水、對照組的外周靜脈血,提取全血基因組DNA、PCR擴(kuò)增目的基因、限制性內(nèi)切酶酶切PCR產(chǎn)物、瓊脂糖凝膠電泳,獲得NOD2基因的3個SNP(R702W,G908R,P268S)及MCP-1啟動子(A-2518G)基因SNP的基因型。同時收集臨床資料,統(tǒng)計(jì)分析探討NOD2及MCP-1的基因SNP以及血清ALB、TBIL、肝功能分級、血清鈉、PCT與乙肝肝硬化腹水并發(fā)SBP的關(guān)系。結(jié)果:通過PCR技術(shù)得到NOD2基因(R702W,G908R,P268S)三種擴(kuò)增產(chǎn)物,酶切后病例組及對照組G908R、P268S未觀察到突變基因型;R702W僅2例(2/40,0.05%)SBP組觀察到突變型但非SBP組及對照組未觀察到突變型。MCP-1(A-2518G)觀察到三種基因型:SBP組基因型AG明顯高于健康對照組(χ2=10.95,P=0.004);非SBP組GG基因型頻率大于健康對照組(χ2=24.78,P0.001);AG基因型SBP組明顯高于非SBP組,P0.05;非SBP組基因型GG高于SBP組,P0.05;等位基因比較:等位基因A在SBP組明顯高于非SBP組,P0.05;等位基因G在非SBP組明顯高于SBP組,P0.05;等位基因G在SBP組及非SBP組的分布頻率均大于健康對照組18例(30.0%),P0.05,差異均具有統(tǒng)計(jì)學(xué)意義。兩組間的臨床指標(biāo)比較結(jié)果提示:血清ALB、TBIL、肝功能分級,血清鈉、PCT差異具有統(tǒng)計(jì)學(xué)意義,P0.05。性別、年齡、凝血酶原時間(Prothrombin time,PT)、丙氨酸氨基轉(zhuǎn)移酶(Alanine aminotransferase,ALT)、天門冬氨酸氨基轉(zhuǎn)移酶(Aaspartate aminotransferase,AST)兩組間沒有統(tǒng)計(jì)學(xué)意義。結(jié)論:1.NOD2二種SNP(G908R,P268S)基因型在漢族人群80例乙肝肝硬化患者及30例對照組中未觀察到突變型,雖然SBP組有2例(2/40,0.05%)R702W突變SNP但沒有統(tǒng)計(jì)學(xué)意義,提示NOD2三種SNP(G908R、P268S、R702W)基因型可能均不是所研究漢族人群乙肝肝硬化腹水并發(fā)SBP的易感基因型,而MCP-1(A2518G)AG基因型和A等位基因可能增加漢族人群乙肝肝硬化腹水并發(fā)SBP的發(fā)生率,對攜帶AG基因型及A等位基因乙肝肝硬化腹水患者臨床綜合評估后可以考慮盡早進(jìn)行治療。2.血清ALB、TBIL、血清鈉、PCT、Child-Pugh分級C級均為乙肝肝硬化自發(fā)性腹膜炎發(fā)生的影響因素。
[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鐨勫叧緋,

本文編號:1577892

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