本文選題：慢性乙型肝炎　切入點：白介素6單核苷酸多態(tài)性　出處：《安徽醫(yī)科大學》2014年碩士論文　論文類型：學位論文

【摘要】：目的：通過研究白介素-6（IL-6）基因中四個標簽單核苷酸多態(tài)性：rs2069852,rs2066992，rs2069837和rs17147230，探討在中國漢族人群中，白介素6與慢性乙型肝炎病毒易感性之間的關系。 方法：收集慢性乙型肝炎患者血標本與急性自限性HBV感染恢復期患者外周血標本作為病例組與對照組。病例組有501例，對照組有301例�；颊哐獦吮镜氖占瘯r間為2011年12月到2012年9月，血標本的采集地點為：安醫(yī)大第一附屬醫(yī)院感染科與安醫(yī)大第二附屬醫(yī)院肝病科。采用酚/氯仿技術，從所有全血標本中提取基因組DNA，找到漢族人群(來自Hapmap數據庫)中IL-6基因中的四個標簽單核苷酸：rs17147230,rs2066992，，rs2069837和rs2069852，然后采用多重單堿基延伸SNP分型技術來對IL-6基因的四個SNPs位點進行分型，最后使用數學統(tǒng)計分析軟件分析出基因型頻率，等位基因頻率、兩位點間的連鎖不平衡系數與單體型頻率，進而得到這四個位點與慢性乙型肝炎的關系。 結果：(1)結果顯示IL-6的5種單體型頻率0.03,為ATAA、TGAG、TGGG、TTAA和TTAG，在病例組的頻率分別為52.55%、8.89%、17.18%、11.79%、6.99%；對照組分別為51.00%、7.64%、15.95%、16.78%、5.65%。分析顯示單體型ATAA、TGAG、TGGG和TTAG無明顯統(tǒng)計學意義，而單體型TTAA有統(tǒng)計學意義。P值分別為ATAA，P=0.6051，OR[95%可信區(qū)間(CI)]=1.056(0.860-1.297); TGAG,P=0.385, OR(95%CI)=1.179(0.813-1.709); TGGG, P=0.549,OR(95%CI)=1.087(0.827-1.429); TTAA, P=0.004, OR(95%CI)=0.655(0.491-0.873);TTAG, P=0.266, OR(95%CI)=1.272(0.832-1.944)。 (2) IL-6基因rs17147230位點的三個基因型AA、AT和TT頻率在病例組分別為30.94%、48.10%、20.96%，對照組分別為28.24%、51.50%、20.27%。rs2066992位點的基因型GG、GT和TT頻率在病例組分別為8.98%、37.92%、53.09%，對照組分別為6.64%、39.20%、54.15%。rs2069837位點的基因型AA、AG和GG頻率在病例組分別為66.07%、30.14%、3.79%，對照組分別為67.11%、28.57%、4.32%。rs2069852位點的基因型AA、AG和GG頻率在病例組分別為41.52%、45.71%、12.77%，對照組分別為45.85%、43.85%、10.30%。結果分析顯示四個位點的基因型在病例組與對照組均無明顯統(tǒng)計學意義，P值分別為(rs17147230, P=0.625;rs2066992, P=0.500; rs2069837, P=0.853; rs2069852, P=0.380)。 (3)統(tǒng)計分析顯示IL-6基因rs17147230位點的等位基因A、T頻率在病例組分別為54.99%、45.01%，對照組分別為53.99%、46.01%。rs2066992位點的等位基因G、T頻率在病例組分別為27.94%、72.06%，對照組分別為26.25%、73.75%。rs2069837位點的等位基因A、G頻率在病例組分別為81.14%、18.86%，對照組分別為81.40%、18.60%。rs2069852位點的等位基因A、G頻率在病例組分別為64.37%、35.63%，對照組分別為67.77%、32.23%。通過以上四個等位基因頻率的對比研究得出病歷組與對照組在統(tǒng)計學上沒有明顯意義。P值分別為rs17147230，P=0.6959， OR(95%CI)=1.0413(0.8500-1.2756)； rs2066992， P=0.4598，OR(95%CI)=1.0898(0.8676-1.3689)；rs2069837，P=0.8982，OR(95%CI)=0.9832(0.7587-1.2742)；rs2069852P=0.165，OR(95%CI)=0.859(0.693-1.064)。 結論：中國漢族人群中IL-6基因tagSNPs rs17147230，rs2066992，rs2069837和rs2069852位點基因多態(tài)性可能與慢性HBV感染的基因易感性有關。
[Abstract]:Objective: To explore the relationship between interleukin 6 and susceptibility to chronic hepatitis B virus in Chinese Han population by studying four label single nucleotide polymorphisms in the interleukin -6 (IL-6) gene: rs2069852, rs2066992, rs2069837 and rs17147230.
Methods: collected blood samples and chronic hepatitis B patients with acute self recovery patients with peripheral blood infection limited HBV as case group and control group. Cases were 501 cases, 301 cases in the control group. Blood samples were collected for the time from December 2011 to September 2012, the blood specimen collection sites for infectious diseases, and the the Second Affiliated Hospital of Anhui Medical University liver diseases department of the First Affiliated Hospital of Anhui Medical University. By using phenol / chloroform extraction technique, the genomic DNA from all the blood samples, found in Han population (from the Hapmap database) in four tag single nucleotide in the IL-6 gene: rs17147230, rs2066992, rs2069837 and rs2069852, then using multiple single nucleotide extension SNP typing technique the four SNPs loci of IL-6 gene typing, and finally the use of mathematical statistical analysis software to analyze the genotype frequency and allele frequency, two locus linkage disequilibrium coefficient and Haplotype frequency, and then the relationship between these four loci and chronic hepatitis B.
Results: (1) the results showed that IL-6 5 haplotype frequencies 0.03, ATAA, TGAG, TGGG, TTAA and TTAG in case group, the frequencies were 52.55%, 8.89%, 17.18%, 11.79%, 6.99%; the control group were 51%, 7.64%, 15.95%, 16.78%, 5.65%. analysis showed that ATAA haplotype, TGAG TGGG, and TTAG was not statistically significant, while haplotype TTAA was statistically significant.P values were ATAA, P=0.6051, OR[95% CI (CI)]=1.056 (0.860-1.297); TGAG, P=0.385, OR (95%CI) =1.179 (0.813-1.709); TGGG, P=0.549, OR (95%CI) =1.087 (TTAA, 0.827-1.429); P=0.004, OR (95%CI) =0.655 (0.491-0.873); TTAG, P=0.266, OR (95%CI) =1.272 (0.832-1.944).
(2) three genotype AA IL-6 gene loci of rs17147230, AT and TT frequency in case group were 30.94%, 48.10%, 20.96%, the control group were 28.24%, 51.50%, GG genotype of 20.27%.rs2066992 locus, GT and TT frequency in case group were 8.98%, 37.92%, 53.09%, the control group were 6.64% 39.20%, AA 54.15%.rs2069837, gene loci, AG and GG frequency in case group were 66.07%, 30.14%, 3.79%, the control group were 67.11%, 28.57%, AA genotype of 4.32%.rs2069852 locus, AG and GG frequency in case group were 41.52%, 45.71%, 12.77%, the control group were 45.85%, 43.85%, 10.30%. the results of analysis showed that the genotype of four loci in the case group and control group were statistically significant, P = (rs17147230, P=0.625; rs2066992, P=0.500; rs2069837, P=0.853; rs2069852, P=0.380).
(3) statistical analysis showed that IL-6 gene rs17147230 allele A, T frequency in case group were 54.99% and 45.01%, the control group was 53.99%, 46.01%.rs2066992 allele G, T frequency in case group were 27.94% and 72.06%, the control group were 26.25%, 73.75%.rs2069837 alleles A, G frequency in case group were 81.14% and 18.86%, the control group was 81.40%, 18.60%.rs2069852 allele A, G frequency in case group were 64.37% and 35.63%, the control group was 67.77%, comparison of 32.23%. through the above four allele frequency of medical group and control group in statistics no significant.P values were rs17147230, P=0.6959, OR (95%CI) =1.0413 (0.8500-1.2756); rs2066992, P=0.4598, OR (95%CI) =1.0898 (0.8676-1.3689); rs2069837, P=0.8982, OR (95%CI) =0.9832 (0.7587-1.2742); rs206 9852P=0.165, OR (95%CI) =0.859 (0.693-1.064).
Conclusion: the tagSNPs rs17147230, rs2066992, rs2069837 and rs2069852 gene polymorphisms of IL-6 gene may be related to the susceptibility of chronic HBV infection in Chinese Han population.

【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R512.62

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