» Articles » PMID: 39139567

Altered Levels of IFN-γ, IL-4, and IL-5 Depend on the Rs4986790 Genotype in COPD Smokers but Not Those Exposed to Biomass-burning Smoke

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with tobacco smoking and biomass-burning smoke exposure. Toll-like receptor 4 () single-nucleotide polymorphisms (SNPs) may contribute to its pathogenesis. The study aimed to assess the association of rs4986790 and rs4986791 in the gene in a Mexican mestizo population with COPD secondary to tobacco smoking (COPD-TS) and biomass-burning smoke (COPD-BBS) and to evaluate whether the genotypes of risk affect cytokine serum levels.

Materials And Methods: We enrolled 2,092 participants and divided them into two comparisons according to their environmental exposure. SNPs were genotyped using TaqMan probes. Serum cytokine levels (IL-4, IL-5, IL-6, IL-10, and INF-γ) were quantified by ELISA.

Results: The rs4986790 AA genotype in COPD-TS was associated with a higher COPD risk (OR = 3.53). Haplotype analysis confirmed this association, identifying a block containing the rs4986790 allele (A-C, OR = 3.11). COPD-TS exhibited elevated IL-6, IL-4, and IL-5 levels compared with smokers without COPD (SWOC), whereas COPD-BBS displayed higher IFN-γ, IL-6, and IL-10 levels. The AA carriers in the COPD-TS group had elevated IL-4, IL-5, and IFN-γ compared with carriers of AG or GG.

Conclusion: The rs4986790 common allele and the A-C haplotype (rs4986790-rs4986791) were associated with a higher COPD risk in smokers; COPD patients carrying the AA genotype showed increased pro-inflammatory cytokines.

References
1.
Wang P, Han X, Mo B, Huang G, Wang C . LPS enhances TLR4 expression and IFN‑γ production via the TLR4/IRAK/NF‑κB signaling pathway in rat pulmonary arterial smooth muscle cells. Mol Med Rep. 2017; 16(3):3111-3116. PMC: 5547977. DOI: 10.3892/mmr.2017.6983. View

2.
Li Z, Mao X, Liu Q, Song H, He B, Shi P . Functional variations of the TLR4 gene in association with chronic obstructive pulmonary disease and pulmonary tuberculosis. BMC Pulm Med. 2019; 19(1):184. PMC: 6805358. DOI: 10.1186/s12890-019-0939-y. View

3.
Zuo L, Lucas K, Fortuna C, Chuang C, Best T . Molecular Regulation of Toll-like Receptors in Asthma and COPD. Front Physiol. 2015; 6:312. PMC: 4637409. DOI: 10.3389/fphys.2015.00312. View

4.
Tang W, Rong Y, Zhang H, Zhan Z, Yuan L, Ning Y . The correlation between a Th1/Th2 cytokines imbalance and vitamin D level in patients with early chronic obstructive pulmonary disease (COPD), based on screening results. Front Physiol. 2023; 14:1032786. PMC: 10063780. DOI: 10.3389/fphys.2023.1032786. View

5.
Rohde G, Klein W, Arinir U, Hagedorn M, Duerig N, Bauer T . Association of the ASP299GLY TLR4 polymorphism with COPD. Respir Med. 2005; 100(5):892-6. DOI: 10.1016/j.rmed.2005.08.018. View