【作者】 胡以松；

【导师】 叶冬青； 李向培；

【作者基本信息】 安徽医科大学 ， 流行病与卫生统计学， 2003， 硕士

【摘要】 目的 探索-2518MCP-1、SDF1-3’A和CCR2-64I基因多态性与系统性红斑狼疮的易感性及临床表型相关性，并分析SLE的环境危险因素及其与-2518MCP-1、SDF1-3’A和CCR2-64I基因多态性的交互作用对SLE发病的影响。 方法 采用病例对照方法探讨2518MCP-1、SDF1-3’A和CCR2-64I基因多态性与SLE发病及临床表型关联性。采取酚—氯仿抽提法提取白细胞中的基因组DNA，运用PCR-RFLP方法确定SDF1-3’A和-2518MCP-1基因多态性，CCR2-64I基因多态性利用ARMS方法确定。用单因素和多因素非条件logistic模型分析影响SLE发病的因素及基因-环境交互作用。 结果 -2518MCP-1、CCR2-64I、SDF1-3’A等位基因及等位基因型频率在SLE和健康对照组之间分布差异均无统计学意义(P均＞0.05)。—2518MCP-1A／G基因型对照组高于病例组(x~2=4.11，P=0.04)，但校正后差异无显著性(Pc=0.12)。SDF1-3’A、-2518MCP-1、CCR2-64I基因间交互作用分析发现，GGAGGG基因型频率对照组高于病例组(P＜0.05)，但校正后差异无显著性(Pc=1.00)。其它基因型间均未见交互作用(P＞0.05)。趋化因子基因多态性与自身抗体相关性分析表明：SDF1-3’A、-2518MCP-1、CCR2-64I基因多态性与系统性红斑狼疮自身抗体的产生均无关。而有关节炎病人中-2518MCP-1G／A基因型频率高于无关节炎病人(P=0.006)，校正后差异仍具有统计学意义(Pc=0.018)，表明-2518MCP-1G／A基因型的SLE病人发生关节炎的可能性更大(OR=3.08，95％CI为1.27～7.57)。三种趋化因子基因多态性与血清中IgG、IgA、IgM、C3、C4、ESR水平以及SLEDAI之间均未见相关性(P＞0.05)。单因素logistic回归分析共发现19个因素与SLE发病有关，多因素logistic模型分析显示有意义的变量共5个，其中喝井水为SLE安徽医科大学硕士学位论文的保护因素(OR=0.o99)，而药物过敏(OR=8.174)、阳光过敏(OR=18.339)、服用抗生素(oR=5.626)、口服避孕药(oR=16.897)为sLE发病的危险因素。非条件logistic模型分析发现在SLE发病中好食刺激性食物与一251 SMCP一IG/G基因型存在交互作用(OR二4.387)。结论单个一25 1 SMCP一l、CCRZ一641、SDFI一3’A基因多态性对SLE易感性无直接作用，但它们之间可能存在交互作用。而且一25 1 SMCP一1基因多态性与SLE病人的关节炎发生有关。另外，有多个环境危险因素与系统性红斑狼疮的发病相关，而且一25 1 SMCP一1基因多态性与好食刺激性食物间存在交互作用。更多还原

【Abstract】 Objective To explore the relationship of SDF1-3’A,CCR2-64I and -2518MCP-1 polymorphisms with susceptibility of systemic lupus erythematosus and its clinical phenotype association, and to analyze gene-environmental and gene-gene interaction contributing to systemic lupus erythematosus.Methods Case-control study was used to explore the association between genes polymorphisms with susceptibility of systemic lupus erythematosus and its clinical phenotype association. Genomic DNA in the leukocyte was extracted by the phenol-trichloromethane extraction method. The polymorphisms of SDF1-3’A, -2518MCP-1 and CCR2-64I were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system(ARMS) Respectively. The environmental factors for SLE were analyzed by univariate and multivariate unconditional logistic regression. The interaction between environmental factors and polymorphisms of SDF1-3’A, -2518MCP-1 and CCR2-64I contributing to systemic lupus erythematosus was also analyzed by logistic regressionmodel.Results There was no significant difference in distribution of allelic and genotype frequency of SDF1-3’A, -2518MCP-1 and CCR2-64I between patients with SLE and controls. The genotype frequency of -2518MCP-1A/G tended to increase incontrol,but the difference was not significant after being corrected (Pc=0.12). Theanalysis of gene-gene interaction showed that the GGAGGG genotype of control washigher than that of patients with SLE, however, no significant difference was found after being corrected(Pc= 1.00).Analysis on association between chemokinespolymorphisms and autoantibody indicated that no significant relationship was found. Compared with patients without arthritis, the -2518MCP-1G,A genotype frequency was higher in patients with arthritis(Pc=0. 018). It showed that the -2518MCP-1G,A genotype increased the risk of arthritis (OR=3.08,95%CI 1.27-7.57). There was no significant relationships between chemokines polymorphisms and IgG, IgA, IgM, C3, C4 level in serum, ESR, and disease activity of systemic lupus erythematosus. Nineteen factors were found to be associated with systemic lupus erythematosus with univariate unconditional logistic regression. But analyzed with multivariate unconditional logistic regression, only five factors left, in which drinking well water(OR=0.099) was protective factors for SLE , and drug allergy (OR=8.174), sunshine allergy (OR=18.339), taking antibiotics (OR=9.630) and oral contraceptives were risk factors for SLE. The analysis of unconditional logistic regression model showed there was interaction between eating irritable food and -2518MCP-1G,G genotype(OR=4.387).Conclusions There is no direct effect of SDF1-3’A,CCR2-64I and -2518MCP-1 polymorphisms on SLE ,but it is possible that the gene-gene interaction exists. -2518MCP-1 polymorphism may play an important role at onset of arthritis of patients with systemic lupus erythematosus. Many environmental factors are related to onset of systemic lupus erythematosus, and there is an interaction between ?2518MCP-1G,G genotype and eating irritable food.更多还原