IL-6基因多态性与慢性HBV感染的相关性研究

发布时间：2018-03-11 05:11

本文选题：慢性乙型肝炎　切入点：白介素6单核苷酸多态性　出处：《安徽医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：通过研究白介素-6（IL-6）基因中四个标签单核苷酸多态性：rs2069852,rs2066992，rs2069837和rs17147230，探讨在中国汉族人群中，白介素6与慢性乙型肝炎病毒易感性之间的关系。方法：收集慢性乙型肝炎患者血标本与急性自限性HBV感染恢复期患者外周血标本作为病例组与对照组。病例组有501例，对照组有301例。患者血标本的收集时间为2011年12月到2012年9月，血标本的采集地点为：安医大第一附属医院感染科与安医大第二附属医院肝病科。采用酚/氯仿技术，从所有全血标本中提取基因组DNA，找到汉族人群(来自Hapmap数据库)中IL-6基因中的四个标签单核苷酸：rs17147230,rs2066992，，rs2069837和rs2069852，然后采用多重单碱基延伸SNP分型技术来对IL-6基因的四个SNPs位点进行分型，最后使用数学统计分析软件分析出基因型频率，等位基因频率、两位点间的连锁不平衡系数与单体型频率，进而得到这四个位点与慢性乙型肝炎的关系。结果：(1)结果显示IL-6的5种单体型频率0.03,为ATAA、TGAG、TGGG、TTAA和TTAG，在病例组的频率分别为52.55%、8.89%、17.18%、11.79%、6.99%；对照组分别为51.00%、7.64%、15.95%、16.78%、5.65%。分析显示单体型ATAA、TGAG、TGGG和TTAG无明显统计学意义，而单体型TTAA有统计学意义。P值分别为ATAA，P=0.6051，OR[95%可信区间(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位点的三个基因型AA、AT和TT频率在病例组分别为30.94%、48.10%、20.96%，对照组分别为28.24%、51.50%、20.27%。rs2066992位点的基因型GG、GT和TT频率在病例组分别为8.98%、37.92%、53.09%，对照组分别为6.64%、39.20%、54.15%。rs2069837位点的基因型AA、AG和GG频率在病例组分别为66.07%、30.14%、3.79%，对照组分别为67.11%、28.57%、4.32%。rs2069852位点的基因型AA、AG和GG频率在病例组分别为41.52%、45.71%、12.77%，对照组分别为45.85%、43.85%、10.30%。结果分析显示四个位点的基因型在病例组与对照组均无明显统计学意义，P值分别为(rs17147230, P=0.625;rs2066992, P=0.500; rs2069837, P=0.853; rs2069852, P=0.380)。 (3)统计分析显示IL-6基因rs17147230位点的等位基因A、T频率在病例组分别为54.99%、45.01%，对照组分别为53.99%、46.01%。rs2066992位点的等位基因G、T频率在病例组分别为27.94%、72.06%，对照组分别为26.25%、73.75%。rs2069837位点的等位基因A、G频率在病例组分别为81.14%、18.86%，对照组分别为81.40%、18.60%。rs2069852位点的等位基因A、G频率在病例组分别为64.37%、35.63%，对照组分别为67.77%、32.23%。通过以上四个等位基因频率的对比研究得出病历组与对照组在统计学上没有明显意义。P值分别为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)。结论：中国汉族人群中IL-6基因tagSNPs rs17147230，rs2066992，rs2069837和rs2069852位点基因多态性可能与慢性HBV感染的基因易感性有关。
[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.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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