Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.
Department of Pulmonary Medicine, Government Medical College, Patiala, India.
Free Radic Biol Med. 2024 Oct;223:118-130. doi: 10.1016/j.freeradbiomed.2024.07.030. Epub 2024 Jul 31.
Chronic Obstructive Pulmonary Disease (COPD) is a persistent inflammatory lung condition characterized by an obstruction in removing oxygen from the lungs. Oxidant and antioxidant imbalance have long been hallmarks of COPD development, where the amount of antioxidants produced is less than that of oxidants. Here, polymorphism in the antioxidant enzymes like Catalase, Superoxide dismutase and Glutathione peroxidase plays an essential role in regulating the levels of oxidants.
1000 subjects, including 500 COPD cases and 500 controls, have been recruited and genotyped to assess the correlation between COPD and the particular SNPS of antioxidant genes. Logistic regression was used to compute odds ratios (ORs) and 95 % confidence intervals (CIs) to assess the association between SNPs and COPD risk. The relationship between spirometry value and COPD for all SNPs has been analyzed using Kruskal Wallis's. Haplotype analysis has also been performed. The effect of SNP interactions on COPD risk was assessed through the Multifactor Dimensionality Reduction (MDR) approach, a nonparametric test for overcoming some of the limitations of the logistic regression for detecting and characterizing SNP interactions.
Our findings indicated a strong association between COPD and the variations in the CAT rs7943316 (OR = 0.61, Pc = 0.0001), SOD2 rs4880 (OR = 2.07, Pc = 0.0006), and GPx rs1050450 (OR = 0.60, Pc = 0.0018). Furthermore, SOD2 rs4880 was associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) of COPD patients. Our study found that the triple combination of SOD1 (rs2234694), SOD1 (rs36232792) and SOD2 (rs4880) was found to be elevating the risk of COPD (OR = 2.83, Pc = 0.006). SOD2 rs4880 and GPx rs1050450 are also linked to cough and mucus production. The Haplotype study reveals a substantial relationship between CAT (rs7943316 and rs1001179) and SOD (rs2234694 and rs4880), which increases the risk of COPD. The three-locus model (CAT rs794331, CAT rs1101179, and GPx rs1050450) was the most effective for COPD risk assessment based on the MDR findings, which were statistically significant (p < 0.0001).
This study shows that rs7943316, rs4880, and rs1050450 are associated with the risk of COPD in the north Indian population and have the potential to enhance our knowledge of COPD at the molecular level, which in turn might pave the way for earlier detection, treatment, and preventive efforts.
慢性阻塞性肺疾病（COPD）是一种以肺部氧气清除受阻为特征的持续性肺部炎症性疾病。氧化应激和抗氧化失衡一直是 COPD 发展的标志，产生的抗氧化剂数量少于氧化剂。在这里，抗氧化酶（如过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶）的基因多态性在调节氧化剂水平方面起着重要作用。
共招募了 1000 名受试者，包括 500 名 COPD 病例和 500 名对照，对这些受试者进行基因分型，以评估 COPD 与抗氧化基因特定 SNP 之间的相关性。使用逻辑回归计算比值比（OR）和 95%置信区间（CI），以评估 SNP 与 COPD 风险之间的关联。使用 Kruskal-Wallis 检验分析所有 SNP 与 COPD 之间的肺活量值关系。还进行了单体型分析。使用多因素维度减少（MDR）方法评估 SNP 相互作用对 COPD 风险的影响，这是一种非参数检验，用于克服逻辑回归在检测和表征 SNP 相互作用方面的一些局限性。
我们的研究结果表明，CAT rs7943316（OR=0.61，Pc=0.0001）、SOD2 rs4880（OR=2.07，Pc=0.0006）和 GPx rs1050450（OR=0.60，Pc=0.0018）的变异与 COPD 之间存在很强的关联。此外，SOD2 rs4880 与 COPD 患者的用力肺活量（FVC）和 1 秒用力呼气量（FEV1）有关。我们的研究发现，SOD1（rs2234694）、SOD1（rs36232792）和 SOD2（rs4880）的三联组合被发现会增加 COPD 的发病风险（OR=2.83，Pc=0.006）。SOD2 rs4880 和 GPx rs1050450 也与咳嗽和黏液产生有关。单体型研究揭示了 CAT（rs7943316 和 rs1001179）和 SOD（rs2234694 和 rs4880）之间存在显著关系，这增加了 COPD 的发病风险。基于 MDR 研究，三基因座模型（CAT rs794331、CAT rs1101179 和 GPx rs1050450）是 COPD 风险评估最有效的模型，其统计学意义显著（p<0.0001）。
本研究表明，rs7943316、rs4880 和 rs1050450 与印度北部人群 COPD 发病风险相关，并有可能提高我们对 COPD 的分子水平认识，从而为早期发现、治疗和预防努力铺平道路。
