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塞尔维亚人群中I期和II期基因功能变异与慢性阻塞性肺疾病的关联

Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population.

作者信息

Stanković Marija, Nikolić Aleksandra, Tomović Andrija, Mitić-Milikić Marija, Nagorni-Obradović Ljudmila, Petrović-Stanojević Nataša, Radojković Dragica

机构信息

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.

Novartis International AG, Novartis Campus, Forum 1, Basel, Switzerland.

出版信息

J Med Biochem. 2015 Apr;34(2):207-214. doi: 10.2478/jomb-2014-0024. Epub 2015 Mar 3.

Abstract

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population.

METHODS

The genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants.

RESULTS

Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025).

CONCLUSIONS

These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.

摘要

背景

慢性阻塞性肺疾病(COPD)是一种以氧化应激增加为特征的复杂疾病。I期和II期基因的功能性遗传变异与氧化剂 - 抗氧化剂失衡有关,可能参与COPD的发生发展。在本研究中,我们旨在调查细胞色素P450(CYP)、谷胱甘肽S - 转移酶(GST)和微粒体环氧化物水解酶(mEH)功能性变异在塞尔维亚人群COPD发病机制中的作用。

方法

测定了122例COPD患者和100例肺功能正常对照者的CYP1A1 *1A/*2A、CYP2E1 *1A/*5B、GSTM1缺失、GSTT1缺失、GSTP1 Ile105Val、mEH Tyr113His和mEH His139Arg基因变异的基因型。

结果

所得结果显示,GSTM1缺失变异在COPD患者中的比例显著高于对照组(61.5%对47.0%;OR = 1.80;p = 0.042)。此外,观察到GSTM1缺失与GSTP1 105Val/(Val)组合存在显著差异(38.5%对24.0%;OR = 1.98;p = 0.029),以及CYP1A1 *1A/*2A、GSTM1缺失和mEH 113His/(His)基因型存在显著差异(7.4%对1.0%;OR = 7.88;p = 0.025)。

结论

这些是关于塞尔维亚人群COPD发病机制中I期和II期基因变异分析的首批数据。本研究所得结果为在更大队列中深入分析遗传因素在COPD中的作用开辟了可能性。此外,它们表明了先前描述的与COPD的遗传关联在我们人群中的重要性,并揭示了一个迄今为止未报道的新关联。

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