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目的:分析白介素(IL)等细胞因子与纤维蛋白原(Fg)Bβ链-1420G/A、-993C/T、1689T/G、BsmAIG/C、I6I/D、345C/T、HinfIA/C 7个基因多态性位点的关系及其对血浆Fg浓度和分子活性系列指标的影响。方法:采用整群抽样方法选取开滦集团离退休职工864人进行体检和问卷调查,抽取静脉血检测血生化及血高敏C反应蛋白(hsCRP)、肿瘤坏死因子(TNF-α)和IL-6、IL-8、IL-10,同时测定血浆Fg浓度和纤维蛋白单体聚合反应速率(FMPV)、最大光密度(Amax)、FMPV/Amax等反映Fg分子聚合功能指标,并应用等位基因特异性聚合酶联反应(AS-PCR)和限制性内切酶片段长度多态性技术及直接基因测序分析检测上述7位点的基因多态性。结果:FgBβHinfI为AC+CC型人群TNF-α水平高于AA人群(P<0.05),其他细胞因子在各位点野生基因型与变异基因型组间均无显著性差异(P>0.05)。以FMPV/Amax为因变量进行多元逐步回归分析,依次筛选出年龄、HDL、UA、hsCRP、口服阿司匹林,标准回归系数(β)为-0.089、-0.094、-0.098、0.091、-0.081(P<0.05);以IL-6为因变量则筛选出IL-8、性别、糖尿病史、TNF-α及HinfI基因型,β分别为0.277、-0.136、0.134、0.125、-0.088(P<0.05);以TNF-α为因变量,则筛选出IL-10、IL-6、BsmAI、UA、1689位点,β分别为0.157、0.127、0.202、0.089、-0.130(P<0.05)。结论:白介素、TNF-α等细胞因子水平与FgBβ链基因多态性具有很强的关联性,它们可以通过影响FgBβ链某些位点的白介素反应元件而具有潜在的调节人类血浆Fg浓度和分子活性表达水平的作用。
OBJECTIVE: To analyze the relationship between interleukin (IL) and other cytokines and fibrinogen (Fg) Bβ chain -1420G / A, -993C / T, 1689T / G, BsmAIG / C, I6I / D, 345C / T, HinfIA / Gene Polymorphism Loci and Their Effects on Serum Fg Concentration and Molecular Activity. Methods: A total of 864 retired workers in Kailuan Group were selected by cluster sampling method for physical examination and questionnaire survey. Venous blood samples were collected for determination of blood biochemical and serum hs-CRP, TNF-α and IL-6 , IL-8, IL-10, Fg concentration and FMPV, Amax, FMPV / Amax and so on were also measured. The allele-specific Polymerase chain reaction (AS-PCR) and restriction fragment length polymorphism (PCR-RFLP) and direct gene sequencing analysis were used to detect the polymorphism of these 7 loci. Results: FgBβHinfI was higher in AC + CC group than in AA group (P <0.05). There were no significant differences in other cytokines between genotypes and genotypes at each site (P> 0.05). Multivariate stepwise regression analysis with FMPV / Amax as the dependent variable showed that age, HDL, UA, hsCRP and oral aspirin were sequentially selected and the standard regression coefficients (β) were -0.089, -0.094, -0.098, 0.091, -0.081, 0.05). The genotypes of IL-8, sex, history of diabetes, TNF-αand HinfI were screened by IL-6 as the dependent variable, β = 0.277,0.136,0.134,0.125,0.088 (P <0.05) IL-10, IL-6, BsmAI, UA, 1689 sites were screened with TNF-α as the dependent variable, β = 0.157,0.127,0.202,0.089,0.130 (P <0.05). CONCLUSION: Cytokines such as interleukin and TNF-α have strong correlation with FgBβ gene polymorphism. They may have potential to regulate human plasma Fg concentration and molecules through affecting interleukin (IL) response element in some sites of FgBβ chain The role of active expression level.