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Background <p>COPD causes persistent airflow restriction, oxidative stress, and inflammation. Proteins like MMP9, MMP12, and ADAM33, and antioxidant enzymes such as Glutathione Peroxidase, Superoxide Dismutase, and Catalase are crucial for lung homeostasis, and imbalances increase COPD risk.</p> Methods <p>A case-control study was carried out with 500 healthy controls and 500 COPD patients. We did genotype on several SNPs in CAT, SOD1, SOD2, GPx, MMP9, MMP12, and ADAM33, and further MDR, CART, and logistic regression models were applied to examine gene-gene interactions, pulmonary function tests, and clinical symptoms.</p> Results <p>SNPs associated with higher COPD risk were <i>SOD2</i> rs4880, <i>CAT</i> rs1001179, <i>MMP9</i> rs17576, and <i>ADAM33</i> rs612709. High-order combinations like <i>SOD2</i> rs4880 and <i>ADAM33</i> rs612709 (AOR = 1.44, <i>p</i> = 0.0001) and <i>CAT</i> rs1001179 and <i>ADAM33</i> rs2280091 (AOR = 1.4, <i>p</i> = 0.0009) showed combinatorial effects. The risk of mucus was greatly lowered by numerous SOD2-based combinations, such as <i>ADAM33</i> rs2280091, <i>MMP9</i> rs17576, and <i>MMP12</i> rs2276109. FEV1, FVC, and FEV1/FVC revealed genotype-specific disparities before and after bronchodilator usage. Combinations of <i>SOD2</i> rs4880, <i>ADAM33</i> rs612709, and <i>MMP9</i> rs3918242 changed bronchodilator responses. MDR study exhibited that <i>CAT</i> (rs7943316) was the best single-locus model for risk prediction towards COPD patients. CART analysis showed <i>SOD2</i> (rs4880) to be a disease risk factor.</p> Conclusion <p>This study is the first to show high-order interactions between selected antioxidant and protease gene variations affecting COPD risk and lung function, specifically <i>SOD2 rs4880</i>, <i>CAT rs1001179</i>, and <i>ADAM33 rs612709</i>. The findings support the potential use of combinatorial genetic profiles in risk stratification and personalized therapeutic strategies for COPD.</p>

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High-order single-nucleotide polymorphism interactions between selected anti-oxidant and protease genes influence North Indians’ propensity for chronic obstructive pulmonary disease (COPD) and lung function parameters

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Heena Kansal,
  • Vishal Chopra,
  • Kranti Garg,
  • Siddharth Sharma

摘要

Background

COPD causes persistent airflow restriction, oxidative stress, and inflammation. Proteins like MMP9, MMP12, and ADAM33, and antioxidant enzymes such as Glutathione Peroxidase, Superoxide Dismutase, and Catalase are crucial for lung homeostasis, and imbalances increase COPD risk.

Methods

A case-control study was carried out with 500 healthy controls and 500 COPD patients. We did genotype on several SNPs in CAT, SOD1, SOD2, GPx, MMP9, MMP12, and ADAM33, and further MDR, CART, and logistic regression models were applied to examine gene-gene interactions, pulmonary function tests, and clinical symptoms.

Results

SNPs associated with higher COPD risk were SOD2 rs4880, CAT rs1001179, MMP9 rs17576, and ADAM33 rs612709. High-order combinations like SOD2 rs4880 and ADAM33 rs612709 (AOR = 1.44, p = 0.0001) and CAT rs1001179 and ADAM33 rs2280091 (AOR = 1.4, p = 0.0009) showed combinatorial effects. The risk of mucus was greatly lowered by numerous SOD2-based combinations, such as ADAM33 rs2280091, MMP9 rs17576, and MMP12 rs2276109. FEV1, FVC, and FEV1/FVC revealed genotype-specific disparities before and after bronchodilator usage. Combinations of SOD2 rs4880, ADAM33 rs612709, and MMP9 rs3918242 changed bronchodilator responses. MDR study exhibited that CAT (rs7943316) was the best single-locus model for risk prediction towards COPD patients. CART analysis showed SOD2 (rs4880) to be a disease risk factor.

Conclusion

This study is the first to show high-order interactions between selected antioxidant and protease gene variations affecting COPD risk and lung function, specifically SOD2 rs4880, CAT rs1001179, and ADAM33 rs612709. The findings support the potential use of combinatorial genetic profiles in risk stratification and personalized therapeutic strategies for COPD.