A functional polymorphism in MMP-9 is associated with childhood atopic asthma
A functional polymorphism in MMP-9 is associated with childhood atopic asthma
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DOI：
10.1016/j.bbrc.2006.03.102
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发表时间：
2006-05-26
影响因子：
3.1
通讯作者：
Tamari, M
中科院分区：
文献类型：
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作者：
Nakashima, K;Hirota, T;Tamari, M
虽然MMP-9在炎症和与哮喘相关的结缔组织重塑中起重要作用，但MMP-9多态性的遗传影响尚不清楚。为了研究MMP-9的多态性是否与儿童特应性哮喘相关，我们共鉴定了17个多态性，并进行了与哮喘（n = 290）和对照组（n = 638）的相关性研究。2127 G> T和5546 G> A（R668 Q）与儿童特应性哮喘的风险显著相关（分别为p = 0.0032和0.0016）。在单倍型分析中，我们还发现与单倍型正相关（p = 0.0053）。MMP-9在培养的人支气管上皮细胞中有表达，dsRNA可上调MMP-9的mRNA表达水平。此外，启动子SNP-1590 C> T与2127 G> T存在强连锁不平衡，可增强MMP-9的转录水平。因此，MMP-9基因可能通过功能性遗传多态性参与哮喘的发生。(c)2006爱思唯尔公司All rights reserved.
Although MMP-9 has been suggested to be important in inflammation and in the connective tissue remodeling associated with asthma, the genetic influences of the polymorphisms of MMP-9 are unclear. To examine whether polymorphisms in MMP-9 are associated with childhood atopic asthma, we identified a total of 17 polymorphisms and conducted an association study with asthma (n = 290) and controls (n = 638). 2127G > T and 5546G > A (R668Q) were significantly associated with the risk of childhood atopic asthma (p = 0.0032 and 0.0016, respectively). In haplotype analysis, we also found a positive association with a haplotype (p = 0.0053). MMP-9 was expressed in cultured human bronchial epithelial cells, and the mRNA expression level was upregulated by dsRNA. Furthermore, the promoter SNP-1590C > T, in strong linkage disequilibrium with 2127G > T, enhanced the transcriptional level of MMP-9. Thus, the MMP-9 gene might be involved in the development of asthma through functional genetic polymorphisms. (c) 2006 Elsevier Inc. All rights reserved.