GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study

Int J Chron Obstruct Pulmon Dis. 2024 Feb 22:19:489-500. doi: 10.2147/COPD.S445680. eCollection 2024.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism.

Methods: Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD.

Results: The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05).

Conclusion: In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

Keywords: GSTP1; NLRP3; chronic obstructive pulmonary disease; polymorphism.

MeSH terms

  • Antioxidants
  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Glutathione S-Transferase pi / genetics
  • Humans
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • Polymorphism, Single Nucleotide
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Risk Factors

Substances

  • Antioxidants
  • Glutathione S-Transferase pi
  • GSTP1 protein, human
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human

Grants and funding

This study was supported by the following grants: National Key Research and Development Project of China 2017YFC0907202 (Xinhua Wang); National Natural Science Foundation of China (82260889) (Xuhui Zhang); Central Guided Local Science and Technology Development Funds Project No.22ZY1QA003(Xinhua Wang); 2022 Gansu Province Higher Education Institutions Industry Support Program Project No.2022CYZC-53(Xinhua Wang).