【摘要】：目的：研究探討Toll樣受體9(TLR9)單核苷酸多態(tài)性與HBV感染自發(fā)清除與肝臟炎癥活動(dòng)的相關(guān)性。 方法：收集422名慢性乙型肝炎病毒(hepatitis B virus, HBV)感染者(其中包括有149名乙型肝炎攜帶者、178名慢性乙型肝炎患者以及95名慢性重型乙型肝炎患者)和174名HBV感染自發(fā)清除者,采用TaqMan探針及PCR技術(shù),檢測出TLR9rs187084、rs352139、 rs352140、rs5743836位點(diǎn)的SNPs,分析各組間基因型及等位基因分布是否存在差異；并將慢性HBV感染組按疾病進(jìn)展、炎癥程度、HBV-DNA載量進(jìn)行分組,比較各組間基因型及等位基因分布時(shí)候存在差異；并研究這四個(gè)位點(diǎn)是否存在連鎖不平衡。 結(jié)果：TLR9rs187084、rs352139、rs352140三個(gè)位點(diǎn)在HBV攜帶者與HBV感染自發(fā)清除者之間,其基因型及等位基因分布存在差異(P0.05)。rs187084位點(diǎn)TT、TC基因型和T等位基因的頻率HBV感染自發(fā)清除者明顯高于慢性HBV感染組(P0.05)。在慢性HBV感染患者中rs187084位點(diǎn)TT、TC基因型和T等位基因的頻率慢性乙型肝炎組及慢性重型肝炎組明顯高于HBV攜帶者(P0.05),rs352139位點(diǎn)AA基因型和A等位基因、rs352140位點(diǎn)CC基因型和C等位基因的頻率慢性乙型肝炎組明顯高于HBV攜帶者組。未發(fā)現(xiàn)rs187084、rs352139、rs352140三個(gè)位點(diǎn)SNP分型與肝臟炎癥程度及血清HBV-DNA載量高低有關(guān)聯(lián)。研究還發(fā)現(xiàn)rs5743836位點(diǎn)在本研究人群中不存在基因多態(tài)性。rs187084、rs352139、 rs352140三個(gè)位點(diǎn)之間存在連鎖不平衡。 結(jié)論：1、TLR9基因rs187084、rs35213、rs352140位點(diǎn)基因多態(tài)性與HBV感染的免疫清除功能及肝臟炎癥活動(dòng)有關(guān),但未發(fā)現(xiàn)該三個(gè)位點(diǎn)的基因多態(tài)性與肝臟炎癥嚴(yán)重程度及HBV-DNA載量高低有關(guān)聯(lián)。2、TLR9基因rs5743836位點(diǎn)可能不存在基因多態(tài)性。3、TLR9基因rs187084、rs352139、rs352140位點(diǎn)之間存在連鎖不平衡。
[Abstract]:Aim: to investigate the relationship between Toll like receptor 9 (TLR9) single nucleotide polymorphism (SNP) and spontaneous clearance of HBV infection and hepatic inflammation. Methods: 422 patients with chronic hepatitis B virus (hepatitis B virus, HBV) infection (including 149 hepatitis B carriers, 178 patients with chronic hepatitis B and 95 patients with chronic severe hepatitis B) and 174 patients with spontaneous clearance of HBV infection were collected. TaqMan probes and PCR techniques were used to detect the SNPs at the sites of TLR9rs187084, rs352139, rs352140 and rs5743836, and to analyze whether there were differences in the distribution of genotypes and alleles among the groups. The genotypes and alleles of the four loci were compared, and the linkage disequilibrium of the four loci was studied. Results the genotype and allele distribution of TLR9rs187084 rs352139rs352140 in HBV carriers and HBV infected spontaneous clearance patients were significantly higher than that in chronic HBV infected patients (P0.05). Rs187084 locus TTT TC genotype and T allele spontaneous clearance frequency were significantly higher than those in chronic HBV infection group (P0.05). The frequencies of TTTC genotype and T allele of rs187084 locus in patients with chronic HBV infection were significantly higher in chronic hepatitis B group and chronic severe hepatitis group than in HBV carriers (P0.05). The frequency of alleles in chronic hepatitis B patients was significantly higher than that in HBV carriers. No correlation was found among the three SNP types of rs187084 rs352139rs352140 and the degree of liver inflammation and the level of serum HBV-DNA load. It was also found that there was no gene polymorphism in the rs5743836 locus. Rs187084 rs352139, and the linkage disequilibrium existed among the three rs352140 loci. Conclusion the rs187084 rs35213rs352140 polymorphism of the TLR9 gene is associated with the immune clearance function of HBV infection and the inflammatory activity of the liver. However, no association was found between the polymorphism of the three loci and the severity of liver inflammation and the level of HBV-DNA load. There may be no linkage disequilibrium between the rs5743836 locus of the TLR9 gene and the rs187084rs352139rs352140 locus.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.62

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