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

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:

• chronic obstructive pulmonary disease
• GSTP1
• NLRP3
• polymorphism

Abbreviations

COPD, chronic obstructive pulmonary disease; GSTP1, Glutathione S-transferase P1; NLRP3, NOD-like receptor thermal protein domain associated protein 3; LD, Linkage disequilibrium; GWAS, genome-wide association analysis; SNPs, the single nucleotide polymorphisms; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; MAFs, the minor allele frequencies; PCR, TaqMan real-time polymerase chain reaction.

Acknowledgment

We thank the Institute of Public Health, Gansu University of Traditional Chinese Medicine. We thank the researchers in our laboratory for their guidance on experimental techniques.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

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).