Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease
Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease
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DOI：
10.1183/09031936.01.00102101
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发表时间：
2001-11-01
影响因子：
24.3
通讯作者：
Sekizawa, K
中科院分区：
文献类型：
--
作者：
Hirano, K;Sakamoto, T;Sekizawa, K
蛋白酶/抗蛋白酶失衡是慢性阻塞性肺疾病（COPD）发生发展的最广泛接受的理论。组织金属蛋白酶-2（TIMP-2）基因突变下调其活性，可能导致基质金属蛋白酶活性增加，导致肺基质降解。通过单链构象多态性分析和测序来检查这些变异，发现了两种多态性，+853 G/A和-418 G/C核苷酸取代。在+853位点基因型频率有显著性差异，COPD患者组G等位基因频率显著高于对照组。在-418位点，COPD患者组C等位基因频率也有高于对照组的趋势。+853 G/A核苷酸取代是沉默变体。Sp1结合位点的保守序列中存在-418 G/C置换，这些多态性可能与慢性阻塞性肺疾病的发生、信使核糖核酸的转录和稳定性降低有关，可作为慢性阻塞性肺疾病易感性的遗传标记。
Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of tissue of metalloproteinases-2 (TIMP-2) that downregulate its activity may increase the activities of matrix metalloproteinases and result in the degradation of the lung matrix.Polymorphisms of the TIMP-2 gene were investigated in 88 COPD patients and 40 control subjects. The variations were examined by single-strand conformational polymorphism analysis followed by sequencing.Two polymorphisms were identified, +853 G/A and -418 G/C nucleotide substitutions. There was a significant deviation in the genotypic frequencies at +853 and the allele frequencies for G were significantly higher in the COPD patient group than in the control group. For locus -418, the allele frequencies for C in the COPD patient group also tended to be higher than those in the control group. The +853 G/A nucleotide substitution was a silent variant. The -418 G/C substitution was located in the consensus sequence for the Sp1 binding site.These polymorphisms may be associated with the development of chronic obstructive pulmonary disease, decreasing the transcription and stability of the messenger ribonucleic acid, and available as genetic markers of susceptibility to the disease.