Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility
Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility
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DOI：
10.2147/copd.s213364
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发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Jie, Zhijun
中科院分区：
文献类型：
--
作者：
Du, Yong;Zhang, Hui;Jie, Zhijun
背景资料：慢性阻塞性肺疾病（COPD）是一种进行性肺部疾病，其特征是不完全可逆的气流限制，这与肺气肿和慢性炎症有关。氧化/抗氧化失衡是目前COPD发病机制之一，最近的几项研究试图揭示COPD及其进展的遗传原因。GST、HO-1、SOD-3是COPD发病的重要易感基因。方法：收集300例COPD患者的外周血标本，分为对照组和COPD组。我们对150名COPD患者和150名对照者的这3个基因的4个单核苷酸多态性（SNPs）进行了基因分型，并采用相关分析和多变量logistic回归分析来分析基因多态性及其与COPD相关数量性状的相互作用。结果表明，GSTP 1、HO-1、SOD-3基因多态性在COPD组与对照组间差异有统计学意义，而GST P1、HO-1、SOD-3基因多态性与COPD的不同分期无相关性。此外，多因素逻辑回归分析表明，COPD GST 1-exon 5 SNP和HO-1（GT）n SNP是COPD的高危因素，并且GST 1 exon 5 SNP和HO-1（GT）n SNP之间存在交互作用。GSTP 1外显子5的AG、GG基因型和HO-1（GT）n的L/M*S、L/L基因型与8-iso-PGF（2 α）（8-iso-PGF 2）、丙二醛（MDA）浓度升高和过氧化氢酶（CAT）活性降低有关。
Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by incomplete reversible airflow limitation, which is associated with emphysema and chronic inflammation. Oxidative/antioxidant imbalance is one of the mechanisms of the current pathogenesis of COPD and several recent studies have attempted to uncover genetic causes of COPD and its progression. GST, HO-1, and SOD-3 are important susceptibility genes related to COPD.Methods: A total of 300 blood samples were included in two groups: Control group and COPD group. We genotyped 4 single nucleotide polymorphisms (SNPs) from these 3 genes in 150 COPD patients and 150 controls to analyze genetic polymorphisms and interactions with COPD-related quantitative traits using correlation analysis and multivariate logistic regression analysis.Results: The results indicated that genotype distributions and allele frequencies of GSTP1, HO-1, and SOD-3 were significantly different between the COPD and the control group, while there is no correlation between the polymorphism of GSTP1, HO-1, SOD3, and the different stages of COPD. Furthermore, multivariate logistic regression analysis indicated that COPD GSTP1-exon5 SNP and HO-1 (GT)n SNP are high-risk factors for COPD and there was interaction between GSTP1 exon5 SNPS and HO-1 (GT) n SNP. More important, the genotypes, AG, GG of GSTP1 exon5 and L/M*S, L/L of HO-1 (GT) n associated with increased 8-iso-prostaglandin F (2 alpha) (8-iso-PGF2) and malondialdehyde (MDA) concentration and decreased catalase (CAT) activity.Conclusion: Collectively, this study shows that genetic polymorphisms of GSTP1, HO-1, and SOD-3 are associated with COPD susceptibility.