Genotypes in matrix metalloproteinase 9 are a risk factor for COPD.
Genotypes in matrix metalloproteinase 9 are a risk factor for COPD.
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DOI：
10.2147/copd.2006.1.3.267
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发表时间：
2006
影响因子：
2.8
通讯作者：
Belinsky SA
中科院分区：
文献类型：
--
作者：
Tesfaigzi Y;Myers OB;Stidley CA;Schwalm K;Picchi M;Crowell RE;Gilliland FD;Belinsky SA
越来越多的证据表明基质金属蛋白酶（MMPs）在COPD的发病机制中发挥作用。因此，我们对4个启动子多态性进行了候选基因关联研究，这些启动子多态性已知会改变MMP-1、MMP-2和MMP-9基因的表达水平，而MMP-9外显子6上的Gln279Arg多态性会改变底物结合区。我们研究了385名吸烟超过20包年的男性退伍军人的每个变体和单倍型的相关性，这些退伍军人的COPD状态使用肺活量测定法进行了表征。这些多态性的关联也被检查与肺功能下降的一部分参与者。只有279Arg变体在COPD患者中更常见，纯合变体与COPD风险增加3倍相关。在单倍型分析中，包含249Arg和MMP-9基因内CA启动子多态性的单倍型与风险相关，这表明279Arg或该单倍型上的连锁变异是这种关联的基础。没有发现这种多态性与肺功能下降有关。这些研究表明，MMP-9基因的变异与这组退伍军人的COPD有关。
A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a role in the pathogenesis of COPD. Therefore, we conducted a candidate gene association study of 4 promoter polymorphisms that are known to modify expression levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon 6 of MMP-9 that modifies the substrate-binding region. We examined the association of each variant and haplotypes in 385 male veterans with greater than 20 pack-years of cigarette smoking whose COPD status was characterized using spirometry. The association of these polymorphisms was also examined with decline of pulmonary function in a subset of participants. Only the 279Arg variant was more common in participants with COPD and the homozygous variant was associated with a 3-fold increased risk for COPD. In the haplotype analysis, the haplotype comprising the 249Arg and the CA promoter polymorphism within the MMP-9 gene was associated with risk, suggesting that either 279Arg or a linked variant on this haplotype underlies the association. No association of this polymorphism was found with decline in pulmonary function. These studies show that variants of the MMP-9 gene are associated with COPD in this cohort of veterans.