Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts.
Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts.
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DOI：
10.1186/1465-9921-12-57
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发表时间：
2011-04-27
影响因子：
5.8
通讯作者：
Boezen HM
中科院分区：
文献类型：
--
作者：
van Diemen CC;Postma DS;Siedlinski M;Blokstra A;Smit HA;Boezen HM
基质金属蛋白酶（MMP）和MMP的组织抑制剂（TIMP）的失衡有助于慢性阻塞性肺疾病（COPD）的发展。缺乏在一般人群中调查MMP和TIMP单核苷酸多态性（SNP）与COPD发展和肺功能下降的纵向研究。我们对1390名在普通人群中进行了前瞻性队列研究的白人进行了MMP 1（G-1607 GG）、MMP 2（-1306 C/T）、MMP 9（3个标签SNP）、MMP 12（A-82 G和Asn 357 Ser）和TIMP 1（Phe 124 Phe和Ile 158 Ile）的SNP分型。使用调整混杂因素的线性混合效应模型分析FEV 1下降。X染色体TIMP 1基因的分析根据性别分层。在一个独立的一般人群队列（n = 1152）中重复所有显著相关性。MMP 2 - 1306 TT基因型携带者与野生型携带者相比，FEV 1下降过度（-4.0 ml/yr，p = 0.03）。TIMP 1 Ile 158 Ile预测男性和女性的FEV 1显著过度下降。TIMP 1 Phe 124 Phe仅预测男性的FEV 1显著过度下降，这在第二队列中重复（p = 0.10）。MMP 2和TIMP 1 Ile 158 Ile相关性未被复制。尽管研究力度有限，但我们没有发现与COPD发展的相关性。我们首次表明，TIMP 1 Phe 124 Phe在两个独立的前瞻性队列中导致FEV 1过度下降，尽管在重复队列中没有达到传统的统计学显著性。MMPs中的SNPs显然不会导致一般人群中FEV 1的下降。
An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking. We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152). MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p = 0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development. We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population.
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DOI：
10.1006/bbrc.2001.5936
发表时间：
2001-11-23
影响因子：
3.1
作者：
Minematsu, N;Nakamura, H;Yamaguchi, K
通讯作者：
Yamaguchi, K
DOI：
10.1056/nejmoa0904006
发表时间：
2009-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hunninghake GM;Cho MH;Tesfaigzi Y;Soto-Quiros ME;Avila L;Lasky-Su J;Stidley C;Melén E;Söderhäll C;Hallberg J;Kull I;Kere J;Svartengren M;Pershagen G;Wickman M;Lange C;Demeo DL;Hersh CP;Klanderman BJ;Raby BA;Sparrow D;Shapiro SD;Silverman EK;Litonjua AA;Weiss ST;Celedón JC
通讯作者：
Celedón JC
DOI：
10.1164/rccm.200506-953oc
发表时间：
2005-12-01
影响因子：
24.7
作者：
Ito, I;Nagai, S;Mishima, M
通讯作者：
Mishima, M
影响因子：
3.5
作者：
Joos, L;He, JQ;Sandford, AJ
通讯作者：
Sandford, AJ
影响因子：
9.6
作者：
GLINDMEYER, HW;JONES, RN;WEILL, H
通讯作者：
WEILL, H