Nakashima Kazuko, Hirota Tomomitsu, Obara Kazuhiko, Shimizu Makiko, Doi Satoru, Fujita Kimie, Shirakawa Taro, Enomoto Tadao, Yoshihara Shigemi, Ebisawa Motohiro, Matsumoto Kenji, Saito Hirohisa, Suzuki Yoichi, Nakamura Yusuke, Tamari Mayumi
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Kanagawa 230-0045, Japan.
Biochem Biophys Res Commun. 2006 May 26;344(1):300-7. doi: 10.1016/j.bbrc.2006.03.102.
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.
尽管已有研究表明基质金属蛋白酶-9（MMP-9）在炎症以及与哮喘相关的结缔组织重塑过程中发挥重要作用，但其基因多态性的遗传影响尚不清楚。为了探究MMP-9基因多态性是否与儿童特应性哮喘相关，我们共鉴定出17种多态性，并针对哮喘患者（n = 290）和对照组（n = 638）开展了关联研究。2127G>T和5546G>A（R668Q）与儿童特应性哮喘风险显著相关（p值分别为0.0032和0.0016）。在单倍型分析中，我们还发现某一单倍型呈正相关（p = 0.0053）。MMP-9在培养的人支气管上皮细胞中表达，且双链RNA可上调其mRNA表达水平。此外，与2127G>T处于强连锁不平衡状态的启动子单核苷酸多态性-1590C>T可提高MMP-9的转录水平。因此，MMP-9基因可能通过功能性基因多态性参与哮喘的发病过程。
