【摘要】：目的探討中國漢族人群聚集素及CLU基因多態(tài)性與阿爾茨海默病風(fēng)險性的關(guān)系及作用機制。 方法采用病例-對照研究方法,共入選了104名LOAD患者和性別、年齡與之相匹配的104名健康對照者。應(yīng)用基質(zhì)輔助的激光解析-電離飛行時間質(zhì)譜(MALDI-TOF-MS)技術(shù)檢測CLU基因rs9331888位點單核苷酸多態(tài)性的分布,載脂蛋白E(ApoE)基因多態(tài)性的分布應(yīng)用等位基因特異性的多重PCR技術(shù)(Multi-ARMS)檢測。采用雙抗體夾心的酶聯(lián)免疫吸附法(enzyme linked immunosorbent assay, ELISA)檢測兩組外周血漿聚集素的濃度。采用熒光定量聚合酶鏈反應(yīng)(fluorescent quantitative polymerase chain reaction, FQ-PCR)檢測兩組外周血白細胞中CLU基因mRNA的表達水平。應(yīng)用Pearson的相關(guān)分析探討CLU基因mRNA和聚集素表達水平與AD患者簡易精神狀態(tài)量表評分的相關(guān)性。 結(jié)果兩組間CLU基因rs9331888位點基因的頻率和等位基因的頻率均有顯著差異(P=0.001；P0.001),等位基因G增加了LOAD的發(fā)病風(fēng)險(OR=2.17,95%CI=1.45-3.23,P0.001)；患者組攜帶ApoE ε4等位基因的頻率明顯高于健康組(P=0.012)；病例組血漿聚集素濃度和CLU基因mRNA的表達水平均明顯高于健康組(P=0.01；P=0.007)；兩組中攜帶危險基因型(CG、GG)的人群蛋白和信使的表達水平均低于攜帶正�；蛐�(CC)的人群(P0.001)。外周血漿聚集素濃度與mRNA表達水平均與AD患者簡易精神狀態(tài)量表評分呈負相關(guān)。 結(jié)論CLU基因rs9331888位點單核苷酸多態(tài)性可能是通過影響CLU基因表達而作為LOAD發(fā)病的危險因素。
[Abstract]:Objective to investigate the relationship between polymorphism of agglutinin and CLU gene and risk of Alzheimer's disease in Chinese Han population. Methods A case-control study was conducted in 104 LOAD patients, gender and age matched 104 healthy controls. Matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to detect the distribution of single nucleotide polymorphisms at the rs9331888 site of the CLU gene. The distribution of apolipoprotein E (ApoE) gene polymorphism was detected by allele-specific multiplex PCR (Multi-ARMS). The concentration of plasma aggregin in peripheral blood of two groups was detected by double antibody sandwich enzyme-linked immunosorbent assay (enzyme linked immunosorbent assay, ELISA). The expression of CLU gene mRNA in peripheral blood leukocytes was detected by fluorescence quantitative polymerase chain reaction (fluorescent quantitative polymerase chain reaction, FQ-PCR). The correlation analysis of Pearson was used to investigate the correlation between the expression of CLU gene mRNA and agglutinin and the score of AD mini-mental state scale. Results there were significant differences in the frequency of rs9331888 locus and allele of CLU gene between the two groups (P0. 001, P0. 001). Allele G increased the risk of LOAD (OR=2.17,95%CI=1.45-3.23,P0.001). The frequency of carrying ApoE 蔚 4 allele was significantly higher in patient group than that in healthy group (P0. 012), the plasma concentration of aggregin and the expression level of CLU gene mRNA in patient group were significantly higher than those in healthy group (P0. 01, P0. 007). The expression levels of protein and messenger in both groups were lower than those with normal genotype (CC) (P0.001). There was a negative correlation between the concentration of plasma aggregin and the expression of mRNA in patients with AD. Conclusion the single nucleotide polymorphism at rs9331888 site of CLU gene may be a risk factor for LOAD by influencing the expression of CLU gene.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R749.16

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