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目的探讨肺纤维化相关细胞因子和炎症因子基因多态性与尘肺易感性的关系。方法以确诊的汉族男性壹期尘肺病患者为病例,选择与病例来自同一工作场所、年龄相差不超过5岁、开始接尘时间及累积接尘工龄相差不超过2年的无尘肺病男性接尘工人为对照。采用聚合酶链反应-限制性片断长度多态性方法检测肿瘤坏死因子(TNF)、纤维粘连蛋白(FN)、转化生长因子-β(TGF-β)、白细胞介素-1(IL-1)、IL-6、人类白细胞抗原(HLA)-DRB1和HLA-DQB1的等位基因及基因型,分析其在2组中的分布情况。采用条件logistic回归方程,进行多因素分析。结果单因素分析发现,病例组携带IL-6(-634)CC、FN MspⅠCC、FN HaeⅢb AA和HLA-DRB1*08等位基因频率高于对照组(P<0.05或P<0.01);IL-1α(-889)1/1、TGF-β(-509 CC、+915 GG)、TNF-α(-308)1/1基因型及HLA-DRB1*09、HLA-DQB1*06等位基频率低于对照组(P<0.05或P<0.01);多因素分析发现,IL-1α(-889)1/1和TGF-β(+915)GG为保护因素;HLA-DRB1*08和FN MspⅠCC基因型为危险因素。结论携带IL-6(-634)CC、FN(MspⅠCC、HaeⅢb AA)基因型和HLA-DRB1*08等位基因的接尘者患尘肺病危险性增加;IL-1α(-889)1/1、TGF-β(-509)CC、TGF-β(+915)GG、TNF-α(-308)1/1基因型及HLA-DRB1*09、HLA-DQB1*06等位基因为保护因素。
Objective To investigate the relationship between polymorphisms of lung fibrosis-related cytokines and inflammatory cytokines and susceptibility to pneumoconiosis. Methods One case of pneumoconiosis was diagnosed in Han nationality male. The patients were from the same workplace with the same work-place. The difference of age was less than 5 years old. The dust-free time was less than 2 years. Workers as a control. Tumor necrosis factor (TNF), fibronectin (FN), transforming growth factor-β (TGF-β) and interleukin-1 (IL-1) were detected by polymerase chain reaction- restriction fragment length polymorphism , IL-6, human leukocyte antigen (HLA) -DRB1 and HLA-DQB1 alleles and genotypes were analyzed in two groups of distribution. Using conditional logistic regression equation, multivariate analysis. Results Univariate analysis showed that the frequencies of IL-6 (-634) CC, FN MspⅠCC, FN HaeⅢb AA and HLA-DRB1 * 08 alleles were significantly higher in the case group than those in the control group (P <0.05 or P <0.01) 1α (-889) 1/1, TGF-β (-509 CC, +915 GG), TNF-α (-308) 1/1 genotype and HLA-DRB1 * 09 and HLA-DQB1 * 06 alleles The levels of IL-1α (-889) 1/1 and TGF-β (+915) GG were lower than that of the control group (P <0.05 or P <0.01). The multivariate analysis showed that HLA-DRB1 * 08 and FN MspⅠCC Genotypes are risk factors. CONCLUSION: The risk of pneumoconiosis is increased in those exposed to IL-6 (-634) CC, FN (MspⅠCC, Hae Ⅲ b AA) genotypes and HLA-DRB1 * 08 alleles. IL-1α (-889) , TGF-β (-509) CC, TGF-β (+915) GG, TNF-α (-308) 1/1 genotype and HLA-DRB1 * 09 and HLA-DQB1 * 06 alleles as protective factors.