白介素-16基因多态性与鼻咽癌遗传易感性的研究

发布时间：2018-02-23 13:47

本文关键词： 鼻咽癌白介素-16 单核苷酸多态性 PCR-RFLP 单倍型　出处：《广西医科大学》2010年硕士论文　论文类型：学位论文

【摘要】： 目的:研究白介素(IL)-16基因多态性在广西健康人群及鼻咽癌患者中的分布,探讨IL-16rs11556218T/G、rs4778889T/C、rs4072111C/T三个位点单核苷酸多态性(SNP)与鼻咽癌的遗传易感相关性,进一步阐明NPC在基因水平上的发病机理,以确定IL-16基因多态性在NPC易感性分析中的应用价值。方法:采用病例-对照研究方法,对来自广西地区的75例鼻咽癌患者和75例健康体检者,应用酶联免疫吸附试验(ELISA)双抗体夹心法检测外周血血清IL-16水平,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)及测序法,分别检测rs11556218T/G、rs4778889T/C、rs4072111C/T三个位点的单核苷酸多态性,计算其基因型及等位基因频率。运用PHASE2.0软件对IL-16基因多态性三个SNP进行单倍型构建与分析,用SPSS13.0软件检验各位点Hardy-Weinberg遗传平衡性(HWE)、基因型、等位基因以及各单倍型在鼻咽癌组和对照组间的频率分布差异。以比值比(OR)及其95%可信区间(CI)表示相对风险度。结果: 1、鼻咽癌组IL-16水平为40.22±9.09pg/mL,健康对照组为28.31±5.28pg/mL,两者比较差异有统计学意义(P=0.00)。 2、鼻咽癌组和健康对照组中IL-16基因rs11556218、rs4778889、rs4072111位点的基因型频率已达到遗传平衡,具有群体代表性(P0.05)。 3、rs11556218位点在鼻咽癌组和健康对照组中具有多态性(T→G),基因型TG在两组间的差异有统计学意义(P=0.037),而GG基因型在两组间无统计学意义。较之野生型TT,携带TG基因型个体患NPC风险增加2.05倍(OR=2.05;95%CI, 1.04-4.01);等位基因G在两组间差异有统计学意义(P=0.027),携带G等位基因的个体患NPC风险增加1.79倍(OR=1.79; 95%CI, 1.06-3.01)。rs4778889位点在鼻咽癌组和健康对照组中具有多态性(T→C),但在两组人群中差异无统计学意义(P=0.097);等位基因C在两组间差异无统计学意义(P=0.154)。rs4072111位点在鼻咽癌组和健康对照组中具有多态性(C→T),但在两组人群差异无统计学意义(P=0.627);等位基因T在两组间差异无统计学意义(P=0.674)。 4、75例健康体检者的IL-16三个位点多态性与其他文献报道的亚洲人群分布较一致,与欧洲人群及撒哈拉以南非洲尼日利亚人群有差异。 5、携带rs11556218 G基因型个体的血清IL-16水平表达显著升高。 6、GTT和GCC单倍型可能是NPC发病的遗传危险因素,这两种单倍型在NPC组的分布频率高于对照组,两组比较差异有统计学意义(P=0.020;P=0.024)。结论:广西地区的75例健康人群中存在IL-16 rs11556218T/G、rs4778889T/C、rs4072111C/T三个位点多态性,其频率分布与亚洲人群分布较一致,但与欧洲及撒哈拉以南非洲人群有差异。rs11556218T/G多态性与鼻咽癌的遗传易感性相关,携带TG基因型个体患NPC风险增加2.05倍,携带G等位基因的个体患NPC风险增加1.79倍;rs11556218T/G、rs4778889T/C、rs4072111C/T三个SNP组成的单倍型GTT和GCC与NPC易感性有关。
[Abstract]:Objective: to study the distribution of IL-16 gene polymorphism in Guangxi healthy population and patients with nasopharyngeal carcinoma (NPC), and to investigate the association between IL-16rs11556218T / Gnrs477889T / Cnrs4072111C- / T and genetic susceptibility of nasopharyngeal carcinoma (NPC). To further clarify the pathogenesis of NPC at the gene level to determine the value of IL-16 gene polymorphism in NPC susceptibility analysis. Methods: using a case-control study, 75 patients with nasopharyngeal carcinoma (NPC) and 75 healthy controls were enrolled in this study. The serum IL-16 levels in peripheral blood were detected by Elisa double antibody sandwich method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing were used to detect the single nucleotide polymorphisms at three loci, rs11556218T / rs4778889T / cor rs4072111C / T, respectively. PHASE2.0 software was used to construct and analyze the haplotypes of IL-16 gene polymorphism three SNP, and SPSS13.0 software was used to test the Hardy-Weinberg genetic balance. The frequency distribution of alleles and haplotypes in nasopharyngeal carcinoma (NPC) group and control group were different. The relative risk degree was expressed by ratio ratio (OR) and its 95% confidence interval (CI). Results:. 1. The IL-16 level was 40.22 卤9.09pg / mL in nasopharyngeal carcinoma group and 28.31 卤5.28pg / mL in healthy control group. 2, the genotype frequency of rs11556218rs4778889 rs4072111 of IL-16 gene in nasopharyngeal carcinoma group and healthy control group has reached genetic balance, and it is representative of population P0.05. 3rs11556218 has polymorphism T in nasopharyngeal carcinoma and healthy controls. 鈫扵here was significant difference in genotype TG between the two groups, but there was no significant difference in GG genotype between the two groups. Compared with wild type TTT, the risk of NPC in individuals with TG genotype increased 2.05 times, 1.04-4.01%, and allele G was different between the two groups. The risk of NPC increased by 1.79 times in individuals with G allele; in 95CI1.06-3.01U, rs4778889 loci were polymorphic T in nasopharyngeal carcinoma and healthy controls. 鈫扵here was no significant difference in allele C between the two groups. There was no significant difference in allele C between the two groups. There was no significant difference in allele C between the two groups. There was no significant difference in allele C between the two groups. The allele C was polymorphic in nasopharyngeal carcinoma (NPC) group and healthy control group (P = 0.154n.rs4072111). 鈫扵here was no significant difference in allele T between the two groups, but there was no significant difference in allele T between the two groups (P < 0. 674). The polymorphism of three IL-16 loci in 475 healthy persons was consistent with the Asian population reported in other literatures, and was different from the European population and the Nigerian population in sub-Saharan Africa. 5. The expression of serum IL-16 was significantly increased in individuals with rs11556218 G genotype. 6GTT and GCC haplotypes may be the genetic risk factors of NPC. The distribution frequency of the two haplotypes in the NPC group was higher than that in the control group. The difference between the two groups was statistically significant. Conclusion: IL-16 rs11556218T / G rs4778889T / rs4072111C / T polymorphism exists in 75 healthy people in Guangxi, and its frequency distribution is consistent with that of Asian population. However, there was a significant difference between rs11556218T / G polymorphism and the genetic susceptibility of nasopharyngeal carcinoma (NPC). The risk of NPC in individuals with TG genotype was increased by 2.05 times. Individuals with G allele had an increased risk of NPC by 1.79 times rs11556218T / rs4778889T / rs4072111C / T haplotype GTT and GCC were associated with NPC susceptibility.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.63

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