Genetic polymorphisms of cytochrome p450 and matrix metalloproteinase in chronic obstructive pulmonary disease.
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.
Cheng
Shih-Lung
SL
Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
Yu
Chong-Jen
CJ
Yang
Pan-Chyr
PC
D000368:Aged; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects
D003577:Cytochrome P-450 Enzyme System; D020782:Matrix Metalloproteinases