[慢性阻塞性肺疾病中超氧化物歧化酶基因多态性与功能活性]

[Superoxide dismutase gene polymorphisms and functional activity in chronic obstructive pulmonary disease].

作者信息

Guo Feng, Kuang Jiu-long

机构信息

Department of Respiratory, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2011 Jun;34(6):424-8.

PMID:21781513

Abstract

OBJECTIVE

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 (χ(2) = 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 (χ(2) = 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 (χ(2) = 0.631, P > 0.05; χ(2) = 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.

摘要

目的

探讨超氧化物歧化酶（SOD）基因多态性与慢性阻塞性肺疾病中超氧化物歧化酶活性的相关性。

方法

本研究共纳入114例慢性阻塞性肺疾病患者（慢性阻塞性肺疾病组）和80名健康志愿者（对照组）。采集外周血并提取全血细胞基因组DNA。采用DNA测序和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法检测锰超氧化物歧化酶（Mn-SOD，G5774A）和细胞外超氧化物歧化酶（EC-SOD，G（-4466）T）基因的多态性。收集外周血浆，采用SOD试剂盒测定SOD的功能活性。

结果

患者组[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）]之间Mn-SOD基因型频率（GG、AG、AA）分布差异有统计学意义（χ² = 7.681，P < 0.05）。患者组A等位基因频率（46.1%，105/228）显著高于对照组（35.0%，56/160），携带Mn-SOD A等位基因的受试者患慢性阻塞性肺疾病的可能性更大[比值比（OR）= 1.585，95%可信区间（CI）（1.045 - 2.404），P < 0.05]。Mn-SOD的AA和AG基因型与最严重的慢性阻塞性肺疾病相关（χ² = 12.345，P < 0.01）。患者组EC-SOD基因型频率（GG、GT、TT）分布分别为76.3%（87/114）、22.8%（26/114）、0.9%（1/114），对照组分别为71.3%（57/80）、28.7%（23/80）、0%（0/80）。患者组与对照组EC-SOD基因不同基因型及等位基因频率分布差异均无统计学意义（χ² = 0.631，P > 0.05；χ² = 0.36，P > 0.05）。慢性阻塞性肺疾病患者的SOD活性[（84 ± 17）kU/L]显著低于健康对照组[（109 ± 15）kU/L]。