Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease

Hirano, Kohji; Sakamoto, Tatsuhiko; Uchida, Yoshiyuki; Morishima, Yuko; Masuyama, Kuniko; Ishii, Yukio; Nomura, Akihiro; Ohtsuka, Mieko; Sekizawa, Kiyohisa

doi:10.1183/09031936.01.00102101

Cited by 107 publications

(91 citation statements)

References 19 publications

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“…In this regard, polymorphisms of the TIMP-2 gene were investigated (Table 1). The -418G/C gene polymorphism in the promoter region and the +853G/A polymorphism in exon 3 of the TIMP-2 gene may be associated with the development of COPD, decreasing the transcription and stability of the messenger RNA (Hirano et al 2001). In another recent study in an Egyptian population, the +853G/A polymorphism but not the -418G/C polymorphism was shown to play a significant role in the susceptibility to COPD (Hegab et al 2005b).…”

Section: Gene Polymorphisms Of Matrix Metalloproteinases In Copdmentioning

confidence: 99%

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

et al. 2008

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20-30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.

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Section: Gene Polymorphisms Of Matrix Metalloproteinases In Copdmentioning

confidence: 99%

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

et al. 2008

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“…Sorsby's fundus dystrophy, a rare dominantly inherited degenerative disease of the retina, has been causally related to mutations in the gene encoding for TIMP3 (Weber et al 1994, John et al 1998. In a further small study of 128 patients, TIMP2 polymorphisms have been associated with chronic obstructive lung disease (Hirano et al 2001). However, to date no study on genetic variation in the TIMP genes and coronary artery disease have been reported.…”

Section: Introductionmentioning

confidence: 99%

Premature coronary artery disease shows no evidence of linkage to loci encoding for tissue inhibitors of matrix metalloproteinases

et al. 2003

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Tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3) are naturally occurring inhibitors of matrix metalloproteinases (MMPs). It has been proposed that MMPs have a role in weakening the fibrous cap and subsequent plaque rupture. We hypothesized that TIMP polymorphisms could predispose to premature coronary artery disease. As a first step, we examined the relevant loci using a linkage approach. Sibling pairs recruited for the British Heart Foundation (BHF) Family Heart Study with premature coronary artery disease were examined. Two to three microsatellite markers were examined per TIMP gene. These markers were either intragenic or very close to the locus encoding for the gene. Products were analyzed by capillary gel electrophoresis. Single and multipoint linkage analysis based on the likelihood ratio test was performed using SPLINK and Mapmaker/Sibs software; 417 families were genotyped consisting of 385 sibling pairs, 27 trios, and five sets of four siblings. We were unable to detect linkage of premature coronary artery disease to loci encoding for TIMP1-3. Polymorphisms of the tissue inhibitors of MMP genes do not predispose to premature coronary artery disease in an epidemiologically significant way.

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“…The association of TIMP-2 polymorphisms with COPD has good biological plausibility. As referenced by HIRANO et al [20], there are substantial in vitro and in vivo data to suggest that metalloproteinases may be important in the pathobiochemistry of COPD. The authors also indicate that the results are not due to the confounder of population stratification, although this possibility cannot be completely excluded by the information provided.…”

Section: Jr Hoidalmentioning

confidence: 99%

“…In this issue of the European Respiratory Journal, HIRANO et al [20] suggest for the first time that variants in the tissue inhibitor of metalloproteinases (TIMP)-2 gene predispose to COPD. The phenotype used is pulmonary function, as measured by forced expiratory volume in one second, which is a strong correlate of COPD and, in population studies, is predictive of all-cause mortality [21][22][23].…”

Section: Jr Hoidalmentioning

confidence: 99%

Genetics of COPD: present and future

Hoidal¹

2001

European Respiratory Journal

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Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease

Cited by 107 publications

References 19 publications

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

Premature coronary artery disease shows no evidence of linkage to loci encoding for tissue inhibitors of matrix metalloproteinases

Genetics of COPD: present and future

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