肿瘤坏死因子α和白介素10基因多态性与非霍奇金淋巴瘤易感性的Meta分析

发布时间：2018-07-27 21:41

【摘要】：目的：探讨肿瘤坏死因子α(TNF-α)基因-308GA、白介素10(IL-10)基因-1082AG位点多态与非霍奇金淋巴瘤(Non-Hodgkin's lymphoma,NHL)易感性的关系。方法：系统检索Pubmed. EMBASE、MEDLINE、 ISI Web of Science中文数据库中国生物医学文献数据库(CBM)、中国知网数据库(CNKI)、重庆维普(VIP)数据库和万方数据库等中外文数据库,收集关于TNF-α基因-308GA和IL-10基因-1082AG位点基因多态性与NHL关联的病例对照研究和队列研究,并追踪参考文献利于百度、Google等搜索引擎进行全面检索,检索时间从建库到2013年5月。纳入公开发表的试验设计严谨,试验方法可靠的病例对照和队列研究,并且其结果均可提供提供各基因型在病例和对照中的分布频率或者例数或者比值比(odds ratio, OR)和95%可信区间(95%confidence interval,95%CI),对纳入的研究文献采用量表进行质量评价。本论文所有的研究分析均采用R软件meta程序包进行,分别分析等位基因遗传模型、显性遗传模型、隐性遗传模型、加性遗传模型和超显性遗传模型与NHL的关系,选用OR及其95%CI作为合并效应值。同时进行亚组分析上述五种模型与弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma, DLBCL)和滤泡性淋巴瘤(follicular lymphoma, FNHL)的关系,并且在剔除低质量研究文献后进行敏感性分析。利用漏斗图和Egger's检验来综合评价研究文献的发表偏倚。结果：(1)TNF-α基因-308GA位点多态与NHL的关系：等位基因遗传模型(A allele vs. G allele, OR=1.18,95%CI=[1.04,1.34],P=0.0128)、显性遗传模型(GA+AA vs. GG, OR=1.15,95%CI=[1.01,1.31], P=0.0394).隐性遗传模型(AA vs. GG+GA, OR=1.46,95%CI=[1.12,1.90], P=0.005)、加性遗传模型(AA vs. GG,OR=1.51,95%CI=[1.15,1.99],P=0.0031)均显示会增加NHL的发病风险,而超显性遗传模型(GG+AA vs. GA, OR=0.94,95%CI=[0.84,1.06],P=0.3073)与NHL易感性无关联。基于NHL肿瘤类型的亚组分析,我们分析了DLBCL和FNHL两种NHL亚型与该位点的关系,结果显示在DLBCL亚组中,该位点与DLBCL易感性有关联,但是未发现其与FNHL易感性存在着关联。(2)IL-10基因-1082AG位点多态与NHL的关系：显性遗传模型(AG+GG vs. AA, OR=1.16,95%CI=[1.04,1.30], P=0.0073)会增加NHL的发病风险。基于NHL肿瘤类型的亚组分析,我们分析了DLBCL和FNHL两种NHL亚型与IL-10基因-1082AG位点的关系,结果显示在DLBCL亚组中,显性遗传模型(AG+GG vs. AA, OR=1.25,95%CI=[1.01,1.54], P=0.0363)会增加DLBCL的发病风险,超显性遗传模型(AA+GG vs. AG, OR=0.85,95%CI=[0.73,0.97],P=0.0199),则会降低DLBCL的发病风险；在FNHL亚组中加性遗传模型(GG vs.AA, OR=3.22,95%CI=[2.40,4.32], P0.0001)会增加FNHL的发病风险。结论：(1)TNF基因-308GA多态位点A等位基因可显著增加NHL,特别是DLBCL的发病风险。(2)IL-10基因-1082AG多态位点可能与NHL易感性有关。
[Abstract]:Objective: to investigate the relationship between polymorphism of tumor necrosis factor 伪 (TNF- 伪) gene -308GA, interleukin-10 (IL-10) gene -1082 AG and susceptibility to non Hodgkin's lymphoma (NHL). Methods: Pubmed. were searched systematically. ISI Web of Science Chinese database, Chinese biomedical literature database, (CBM), China knowledge network database, (CNKI), Chongqing Weipu (VIP) database, Wanfang database and other Chinese and foreign language databases, Case control studies and cohort studies on the association of NHL with TNF- 伪 gene -308GA and IL-10 gene -1082AG locus polymorphism were collected. To include publicly published case-control and cohort studies with rigorous design and reliable trial methods, The results can provide the distribution frequency or the number of cases or the ratio of each genotype in the case and control group than (odds ratio, OR) and 95% confidence interval (95%confidence interval-95 CI). The quality evaluation of the included research literature was carried out by using the scale. All the research and analysis in this paper are carried out with R software meta package. The relationships between allele genetic model, dominant genetic model, recessive genetic model, additive genetic model and superdominant genetic model and NHL are analyzed, respectively. OR and its 95%CI were selected as the combined effect value. The relationship between the above five models and diffuse large B-cell lymphoma (diffuse large B cell lymphoma, DLBCL) and follicular lymphoma (follicular lymphoma, FNHL) was analyzed by subgroup analysis. Funnel diagram and Egger's test were used to evaluate the publication bias of the research literature. Results: (1) the relationship between polymorphism of TNF- 伪 gene -308GA locus and NHL: the allelic genetic model (A allele vs. G allele, OR1.18995 CI = [1.04n1.34] PN0.0128), and the dominant genetic model (GA AA vs. GG, OR-1.1595CI = [1.01n1.31], P0.0394). The recessive genetic model (AA vs. GG GA, OR1. 466 / 95 CI = [1.121.90], P0. 005) and additive genetic model (AA vs.) GGG OR1. 51 ~ 95CI= [1. 151.99] P0. 0031) all showed that the risk of NHL was increased, but the overdominance genetic model (GG AA vs. GA, OR0. 949 5CII = [0. 841.06] Pu 0.3073) was not associated with the susceptibility of NHL. Based on the subgroup analysis of NHL tumor types, we analyzed the relationship between DLBCL and FNHL NHL subtypes and this locus. The results showed that in the DLBCL subgroup, this locus was associated with DLBCL susceptibility. (2) the relationship between polymorphism of IL-10 gene -1082AG and NHL: the dominant genetic model (AG GG vs. AA, OR1.16995 CI = [1.04N 1.30], P0. 0073) could increase the risk of NHL. Based on the subgroup analysis of NHL tumor types, we analyzed the relationship between the NHL subtypes of DLBCL and FNHL and the IL-10 gene -1082 AG locus. The results showed that in DLBCL subgroup, the dominant genetic model (AG GG vs. AA, OR1. 25 ~ 95 CI = [1. 01 + 1. 54], Pn0. 0363) increased the risk of DLBCL. The risk of DLBCL was decreased by (AA GG vs. AG, OR0.85 / 95CI = [0.730.97] P0.0199, and the risk of FNHL was increased by the additive genetic model (GG vs.AA, OR3.22C95CI= [2.404.32], P0.0001) in the FNHL subgroup. Conclusion: (1) allele A of TNF gene -308GA polymorphism can increase the risk of NHL, especially the risk of DLBCL. (2) the polymorphism of IL-10 gene -1082 AG may be related to the susceptibility of NHL.
【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R733.1

【参考文献】