The Study On Superoxide Dismutase Gene Polymorphisms And Functional Activity In Chronic Obstructive Pulmonary Disease

Objective:Chronic obstructive pulmonary disease (COPD) is a chronic respiratory system disease characterized by airflow limitation that is not fully reversible, it is a major and increasing cause of morbidity and mortality worldwide and its prevalence is still increasing. Though at the present time, the pathogenesis of COPD is still not understanded, it has been demonstrated by sorts of studies that COPD was a complex disease affected by both the genes and environmental factors. Out of balance between oxidizing and anti-oxidizing, out of balance between protease and anti-protease, including with airway inflammation play an important role in the pathogenesis of COPD. Superoxide dismutases (SODs) are the only one proleases of superfamily which anti-superoxide free radical, they are important antioxidant enzymes to maintain the balance of oxidizing and anti-oxidizing. We study the association of genetic polymorphism of superoxide dismutase and superoxide dismutase activity with chronic obstructive pulmonary disease in order to find out the susceptible gene for COPD and furtherly understand the pathogenesis mechanism, to select the susceptible population to be prevented earlier and reduce the incidence of COPD.Methods:A case-control study research was designed,114 patients of Han nationality with COPD in stable phase were recruited from respiration unit of hospital in Nanchang of Jiangxi from May,2009 to May,2010(the COPD group), all of them are consistent with the diagnoses and treatment guideline of Chronic Obstructive Pulmonary Disease in 2007. We chose 80 healthy volunteers(the control group) from clinic service and the department of health examination. Limosis peripheral blood was taken and whole blood corpuscle genomic DNA was extracted. The genetic polymorphism of Mn-SOD (G5774A) and EC-SOD G(-4466)T genes was determined by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Peripheral blood plasma was collected and the functional activity of SOD was determined by SOD kit. The data of age, body mass index of this study were analyzed by T test, the data of frequency of genetype from different group and allele gene frequency were analyzed by Chi square, the OR and 95%CI was calculated by Logistic regression.Result:The Mn-SOD frequencies of the genotypes (GG, AG, AA) between patients(27.2%,53.5% and 19.3%) and controls(46.3%,37.5% and 16.2%) were significant differences(χ2=7.681, P<0.05). The frequencies of A allele gene in patients(46.1%) were significant higher than in controls (35.0%)[OR=1.585, 95%CI(1.045-2.404), P=0.03], the AA and AG genotypes of Mn-SOD were correlation with the most severely COPD(χ2=12.345, P=0.002<0.01). The EC-SOD frequencies of the genotypes (GG, GT, TT) in COPD was 76.3% ,22.8% and 0.9%; the genotypes frequencies(GG, GT) in controls was 71.3% and 28.7%; the TT genotypes was not found in controls. The EC-SOD frequencies of G and T allele gene was 87.7%,12.3% in COPD group and 85.6%,14.4% in control group. There were no significant differences in the distribution of the different genotypes or allele gene frequencies between patients and controls for the EC-SOD genes(χ2=0.631, P=0.427;χ2=0.361, P=0.548). The SOD activity of COPD patients[(83.7±16.7) U/ml] were significant lower than the healthy controls [(108.7±14.5) U/ml], however, there were no significant differences in the SOD activity of the different genotypes in COPD for the Mn-SOD and EC-SOD genes (F=0.443, P=0.643>0.05;t=1.283, P=0.202>0.05)Conclusion:1.Mn-SOD(G5774A) genetic polymorphism is related to the development of COPD, it may be the COPD-related gene, The Mn-SOD 5774A allele gene may be the predisposing genes of COPD; The AA and AG genotypes of Mn-SOD were correlation with the most severely COPD; 2.The genetic polymorphism of EC-SOD G(-4466)T is not associated with the development of COPD; 3.The decrease of blood plasma SOD activity in COPD patients indicates dysfunction of the oxidant/antioxidant defence system in COPD. The association between SOD activity and the genetic polymorphism of Mn-SOD 5774A and EC-SOD G(-4466)T is indefinite, it suggest the blood plasma SOD activity regulated by varied factors in COPD were complex.