摘要目的 探讨锰超氧化物歧化酶(Mn-SOD)及细胞外超氧化物歧化酶(EC-SOD)基因多态性与血浆中SOD活力及COPD易感性的相关性.方法 收集114例COPD患者(COPD组)和80名健康者(对照组)外周血,提取全血细胞DNA,采用基因测序及限制性片段长度多态性分析检测两组Mn-SOD(G5774A)和EC-SOD G(-4466)T基因多态性;提取外周血血浆,检测2组血浆中SOD活力.结果 COPD组Mn-SOD 的GG、AG和AA基因型频率分别为27.2%(31/114)、53.5%(61/114)和19.3%(22/114),与对照组[46.3%(37/80)、37.5%(30/80)和16.2%(13/80)]比较,差异有统计学意义(χ2=7.681,P<0.05);COPD组A等位基因频率(46.1%,105/228)显著高于对照组(35.0%,56/160),Mn-SOD 5774A等位基因是COPD的易感基因(OR=1.585,95%CI为1.045～2.404,P<0.05);AG和AA基因型与极重度COPD有相关性(χ2=12.345,P<0.01).COPD组EC-SOD的GG、GT和TT基因型频率分别为76.3%(87/114)、22.8%(26/114)和0.9%(1/114),G、T等位基因频率分别为87.7%(200/228)和12.3%(28/228);对照组GG、GT基因型频率分别为71.3%(57/80)和28.7%(23/80),G、T等位基因频率分别为85.6%(137/160)和14.4%(23/160),未检测到TT基因型,2组间基因型及等位基因频率分布比较,差异均无统计学意义(χ2值分别为0.631和0.361,均P>0.05).COPD组SOD活力[(84±17) kU/L]明显低于对照组[(109±15) kU/L].结论 Mn-SOD(G5774A)位点基因多态性可能与COPD的易感性相关,Mn-SOD的5774A等位基因可能是COPD的易感基因,AG和AA基因型与极重度COPD有相关性;COPD患者存在SOD活力下降,提示COPD患者存在氧化/抗氧化失衡.

abstractsObjective To explore the association of genetic polymorphism of superoxide dismutase (SOD) and superoxide dismutase activity in chronic obstructive pulmonary disease. Methods A total of 114 patients with COPD (the COPD group) and 80 healthy volunteers (the control group) were enrolled in this study. Peripheral blood was taken and whole blood cell genomic DNA was extracted. The genetic polymorphisms of Mn-SOD (G5774A) and EC-SOD G (-4466)T genes were 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 a SOD kit. Results The distribution of the Mn-SOD genotype frequencies (GG, AG, AA) between the patients [27.2% (31/114), 53.5% (61/114) and 19.3% (22/114)] and the controls [46.3% (37/80), 37.5% (30/80) and 16.2% (13/80)] were significantly different (χ2=7.681, P<0.05). The A allele gene frequencies of the patients (46.1%, 105/228) were significant higher than those of the controls (35.0%, 56/160), and subjects with the A allele gene of Mn-SOD were more likely to have COPD [OR=1.585, 95%CI (1.045-2.404), P<0.05]. The AA and AG genotypes of Mn-SOD were correlated with the most severe COPD (χ2=12.345, P<0.01). The distribution of the EC-SOD genotype frequencies (GG, GT, TT) was 76.3%(87/114), 22.8%(26/114), 0.9% (1/114) in the patients and 71.3% (57/80), 28.7% (23/80), 0% (0/80) in the controls. The allele gene frequencies of the EC-SOD (G, T) were 87.7% (200/228), 12.3% (28/228) in the patients and 85.6% (137/160), 14.4% (23/160) in the controls. There were no significant differences in the distribution of the different genotypes or allele gene frequencies between the patients and the controls in the EC-SOD genes (χ2=0.631, P>0.05; χ2=0.36, P>0.05). The SOD activity of COPD patients [(84±17) kU/L] was significant lower than that of the healthy controls [(109±15) kU/L]. Conclusions Mn-SOD(G5774A) genetic polymorphism is related to the development of COPD. The Mn-SOD 5774A allele gene may be one of the predisposing genes for COPD. The AA and AG genotypes of Mn-SOD were correlated with the most severy COPD. The decrease of blood plasma SOD activity in COPD patients indicates a dysfunction of the oxidant/antioxidant defense system in the disease.