Genetic Polymorphisms of Cytochrome P450 and Matrix Metalloproteinase in Chronic Obstructive Pulmonary Disease

被引:25
作者
Cheng, Shih-Lung [1 ,2 ,3 ]
Yu, Chong-Jen [1 ]
Yang, Pan-Chyr [1 ]
机构
[1] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 10764, Taiwan
[2] Far Eastern Mem Hosp, Dept Internal Med, Taipei, Taiwan
[3] Yuan Ze Univ, Dept Chem Engn & Mat Sci, Tao Yuan, Taiwan
关键词
Polymorphism; Cytochrome P-450; Matrix metalloproteinase; Pulmonary disease; Chronic obstructive; LUNG-CANCER SUSCEPTIBILITY; RAPID GENOTYPE ANALYSIS; EXPRESSION; CYP1A1; EMPHYSEMA; POPULATION; GSTM1; MATRIX-METALLOPROTEINASE-9; HISTORY; CYP2E1;
D O I
10.1007/s10528-009-9252-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated whether polymorphisms of cytochrome P450 (CYP) and matrix metalloproteinase (MMP) are associated with the development and severity of chronic obstructive pulmonary disease (COPD). Genotypes of 184 patients with COPD and 212 controls were determined by polymerase chain reaction, followed by restriction fragment length polymorphism. The homozygous T allele of MMP-9 was significantly higher in patients with COPD than in controls (14.7% vs. 7.5%). The odds ratio was 2.4 (95% CI 1.1-5.9). No differences were observed in the frequency of polymorphic genotypes in CYP1A1, 1A2, MMP-1 and -3. During combined analysis of these candidate genes, we found strong indicators for susceptibility to COPD (combined with homozygotes *2A for CYP1A1 and T alleles of MMP-9 versus others = 3.3, 95% CI 1.2-8.6). The frequency of the homozygous *2A allele of CYP1A1 was significantly higher in very severe COPD (P < 0.01). Combinations of genetic variants including *2A homozygotes of CYP1A1 and T alleles in MMP-9 are significant indicators for susceptibility to COPD. The homozygous *2A allele of CYP1A1 is an independent risk factor for very severe COPD.
引用
收藏
页码:591 / 601
页数:11
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