Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.
Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.
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DOI：
10.1186/1471-2350-11-7
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发表时间：
2010-01-15
影响因子：
--
通讯作者：
Kalsheker N
中科院分区：
文献类型：
--
作者：
Haq I;Chappell S;Johnson SR;Lotya J;Daly L;Morgan K;Guetta-Baranes T;Roca J;Rabinovich R;Millar AB;Donnelly SC;Keatings V;MacNee W;Stolk J;Hiemstra PS;Miniati M;Monti S;O'Connor CM;Kalsheker N
遗传因素在慢性阻塞性肺疾病（COPD）中发挥作用，但知之甚少。在COPD发病机制的基础上提出了许多候选基因。这些包括基质金属蛋白酶（MMP）基因，其在组织重塑中起作用，并且符合COPD病因的蛋白酶-抗蛋白酶失衡理论。以前的COPD中MMPs的遗传学研究对基因的覆盖不足，并且报告了单核苷酸多态性（SNP）和SNP单倍型的相互矛盾的关联，可能是由于动力不足的研究。为了解决这些问题，我们对来自977名COPD患者和876名欧洲血统的非患病吸烟者的MMP- 1、9和12中的26个SNP进行了基因分型，全面覆盖了报道的SNP变异，并评估了它们与疾病的相关性。我们使用逻辑回归来调整年龄、性别、中心和吸烟史。MMP-12中两个SNP的单倍型（rs652438和rs 2276109）显示与重度/极重度疾病相关，对应于GOLD III期和IV期。具有这两个SNP的共同A-A单倍型的人发生严重/非常严重疾病的风险更大（p = 0.0039），而在任一SNP位点具有次要G变异的人具有保护作用（调整的比值比为0.76; 95%CI 0.61 - 0.94）。A-A单倍型也与FEV 1预测值显著降低相关（42.62%对44.79%; p = 0.0129）。这暗示MMP-12的单倍型作为疾病严重程度的修饰物。
Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.
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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
影响因子：
64.5
作者：
DARMIENTO, J;DALAL, SS;CHADA, K
通讯作者：
CHADA, K
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：
0.4
作者：
Schirmer, H.;da Silva, L. Basso;Simon, D.
通讯作者：
Simon, D.
影响因子：
9.8
作者：
Becker, T;Knapp, M
通讯作者：
Knapp, M