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中国东北地区人群中巨噬细胞移动抑制因子(MIF)启动子多态性与儿童哮喘的关联

Association of MIF promoter polymorphisms with childhood asthma in a northeastern Chinese population.

作者信息

Wu J, Fu S, Ren X, Jin Y, Huang X, Zhang X, Bai J, Fu S

机构信息

Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

出版信息

Tissue Antigens. 2009 Apr;73(4):302-6. doi: 10.1111/j.1399-0039.2008.01206.x.

Abstract

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in pathogenesis of asthma. A high level of MIF has been detected in bronchoalveolar lavage fluid, serum and sputum in asthma. Polymorphisms associated with inflammatory diseases exist in the promoter region of MIF, which alter its expression. The aim of this study was to evaluate the potential relationship between functional polymorphisms of MIF and childhood asthma in a northeastern Chinese population. The study consisted of a set of 41 trios and an independent sample set of 189 childhood asthma patients and 261 healthy controls. We genotyped MIF-173G/C using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Additionally, MIF-794CATT(5-8) microsatellite polymorphism was genotyped by polyacrylamide gel electrophoresis (PAGE). A statistically significant difference in the distribution of the MIF-173C allele between patients and controls [P = 0.01, odds ratio (OR) = 1.55, 95% confidence interval (CI) = 1.13-2.18] was observed. In addition, the frequency of the MIF-173CC genotype was higher in asthmatic children (P < 0.01, OR = 3.37, 95% CI = 1.27-8.93). No difference in the distribution of CATT(5-8) was found between patients and healthy controls. Haplotype analysis showed that only the MIFCATT(7)-173C haplotype was associated with greater susceptibility to childhood asthma (P = 0.03, OR = 1.54, 95% CI 1.03-2.28). However, the transmission disequilibrium test confirmed a positive association between MIF-173G/C and childhood asthma (P = 0.005), and the absence of an association between the MIF-794CATT(5-8) and the disease. These preliminary results suggest an association between the MIF-173C allele and childhood asthma.

摘要

巨噬细胞移动抑制因子(MIF)是一种促炎细胞因子,在哮喘发病机制中起重要作用。在哮喘患者的支气管肺泡灌洗液、血清和痰液中已检测到高水平的MIF。MIF启动子区域存在与炎症性疾病相关的多态性,这些多态性会改变其表达。本研究的目的是评估中国东北人群中MIF功能多态性与儿童哮喘之间的潜在关系。该研究包括一组41个三联体以及一个由189例儿童哮喘患者和261例健康对照组成的独立样本集。我们使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对MIF-173G/C进行基因分型。此外,通过聚丙烯酰胺凝胶电泳(PAGE)对MIF-794CATT(5-8)微卫星多态性进行基因分型。观察到患者与对照之间MIF-173C等位基因分布存在统计学显著差异[P = 0.01,优势比(OR)= 1.55,95%置信区间(CI)= 1.13 - 2.18]。此外,哮喘儿童中MIF-173CC基因型的频率更高(P < 0.01,OR = 3.37,95% CI = 1.27 - 8.93)。患者与健康对照之间未发现CATT(5-8)分布存在差异。单倍型分析表明,只有MIFCATT(7)-173C单倍型与儿童哮喘易感性增加相关(P = 0.03,OR = 1.54,95% CI 1.03 - 2.28)。然而,传递不平衡检验证实MIF-173G/C与儿童哮喘之间存在正相关(P = 0.005),且MIF-794CATT(5-8)与该疾病之间不存在相关性。这些初步结果表明MIF-173C等位基因与儿童哮喘之间存在关联。

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