Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy
Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy
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DOI：
10.1164/rccm.200307-933oc
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发表时间：
2004-05-01
影响因子：
24.7
通讯作者：
Nishimura, M
中科院分区：
文献类型：
--
作者：
Hizawa, N;Yamaguchi, E;Nishimura, M
巨噬细胞迁移抑制因子（MIF）是一种多营养性淋巴细胞和巨噬细胞的细胞因子；它可能在先天免疫中起重要作用。对特应性易感性基因的全基因组搜索最近确定了人类染色体22q11，其中编码MIF的基因所在，作为特应性性状的兴趣区域。MIF启动子区域的-173G/C和-794 [CATT]（5-8）重复多态性都与体外MIF基因转录水平的改变有关。因此，我们假设这些潜在的功能多态性可能影响对特应性和哮喘的易感性。一项病例对照分析检查了这些启动子多态性对日本人群（n = 584）特应性和哮喘发展的遗传影响。发现-173G/C与-794 [CATT]（5-8）重复多态性和特应性之间存在显著关联的证据；-173C等位基因纯合子的比值比为3.67（与-173G等位基因纯合子相比，95%可信区间= 1.43 ~ 946,p < 0.01）， -794 [5-CATT]等位基因非携带者的比值比为3.51（与5-CATT重复等位基因纯合子相比，95%可信区间= 1.82 ~ 6.78,p < 0.0005）。未发现与哮喘相关。这些结果表明，MIF启动子区域的启动子多态性是特应性的危险因素，并暗示MIF与日本人群特应性的发病机制有关。
Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Genome-wide search for atopy susceptibility genes recently identified human chromosome 22q11, where the gene encoding MIF resides, as a region of interest for atopic traits. Both the -173G/C and -794 [CATT](5-8) repeat polymophisms in the MIF promoter region are associated with altered levels of MIF gene transcription in vitro. We therefore, hypothesized that these potentially functional polymorphisms may influence susceptibility to atopy and asthma. A case-control analysis examined the genetic influence of these promoter polymorphisms on the development of atopy and asthma in a japanese population (n = 584). Evidence for significant association between the -173G/C and -794 [CATT)(5-8) repeat polymorphisms and atopy was found; odds ratio for homozygotes of -173C allele was 3.67 (compared with homozy-gotes of -173G allele, 95% confidence interval = 1.43-946, p < 0.01), and odds ratio for noncarriers of the -794 [5-CATT] allele was 3.51 (compared with 5-CATT repeat homozygotes, 95% confidence interval = 1.82-6.78, p < 0.0005). No assocations with asthma were detected. These results indicate that promoter polymorphisms in the MIF promoter region are risk factors for atopy and implicate MIF in the pathogenesis of atopy in a Japanese population.