| Chronic obstructive pulmonary disease (COPD) is a very common respiratory disease which has high morbidity and mortality in the world. Although smoking is considered as the major causal factor in the development of COPD and it was reported that 80-90% COPD patients are cigarette smokers , only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD that suggests the presence of genetic susceptibility. The individual variance of response to airway obstruction and some family history of COPD patients also indicate the important role of genetic predisposition. Among the multiple genetic variants, the germline polymorphisms of genes encoding tobacco detoxification enzymes, protease and anti-protease might impose important affect on the susceptibility of COPD. Matrix Metalloproteinases (MMPs) is a family of proteases and has been suggested to play important roles in the pathogenesis of pulmonary emphysema, especially MMP1 and MMP12. Glutathione S-transferase (GSTM1) is phase II detoxifying enzyme induced in response to oxidative stress, which may occur during smoking. There are germline polymorphisms lying in all of the three genes that can cause significant decrease of enzymes expression and might have solid impact on genetic susceptibility of COPD.To test our hypothesis, a retrospective case-control study was conducted to explore the associations, and then to provide informative evidences and useful methods for high-risk population screening, diagnosis and treatment.Materials and Methods: fifty-nine cases with COPD were recruited from the First Affliated Hospital of Zhengzou University, which were histopathologically confirmed from 2002 to 2003, they all accord with the Golden Guide of COPD, One hundred and nine subjects with matched age and sex frequencies were randomly selected as control group from the same region in the field surveys between year 20002 and 2003. All cases were nan nationality and were investigated to exclude other simultaneous malignancies and lung diseases. Genomic DNA was extracted from blood using protocols provided by Gentra Puregene DNA purification kit. Polymerase Chain Reaction (PCR) and PCR based Restriction Fragment Length Polymorphisms (PCR-RFLP) detection were applied to analyze genotypes of the polymorphisms. Retrospective case-control study was conducted and Fisher Exact x 2 test was adopted to check the accordance with Hardy-Weinberg equilibrium in the control group. For risk estimation, the risk was evaluated in terms of age-sex adjusted odds ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression model. All of the statistical analyses were calculated by SPSS 10.0 statistical software. (p<0.05 was regarded as significant)Results:1. For MMP1, the allele frequencies of 2G were 12% and 73% in control and COP D groups, respectively. For MMP12, the allele frequencies of G were l%and 0 in control and COPD groups, respectively. For GSTM1, the null type frequencies were 53% and 66% in control and COPD groups, respectively.2. The frequencies of MMP1 genotypes distribution were 71.5%^ 20.2% and8.3% for MMP1(2G/2G), MMP1(2G/1G) and MMP1(1G/1G) in controls, respectively; for cases, the frequencies of MMP1(2G/2G), MMP1(2G/1G) and MMP1(1G/1G) were 54.2%, 37.3%and 8.5%in individuals with COPD, respectively. For MMP12,frequencies of the AA and AG were 98.17% and 1.83% respectively in controls, 100% and 0, respectively, in cases with COPD. For GSTM1, frequencies of the wild type and null type were 46.8% and 53.2% respectively in controls, 33.9% and 66.1%, respectively, in cases with COPD. Hardy- Weinberg Equilibrium test was performed on each polymorphism in the control group and the results showed no statistically significant difference .3. Taking the MMP1(1G/1G) genotype and (2G/1G) genotype as a reference group , the sex- and age- adjusted OR for the MMP1(2G/2G) genotype indicated a OR=0.467(95%CI=0.237-0.924), P<0.05 , there was statistically significant difference.4. There was no statistically significant d...
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