HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Front Immunol. 2024 Jul 30;15:1411408. doi: 10.3389/fimmu.2024.1411408. eCollection 2024.
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.
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.
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.
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.
慢性阻塞性肺疾病（COPD）与吸烟和生物质燃烧烟雾暴露有关。Toll 样受体 4（）单核苷酸多态性（SNP）可能与其发病机制有关。本研究旨在评估在墨西哥梅斯蒂索人群中，与吸烟引起的 COPD（COPD-TS）和生物质燃烧烟雾引起的 COPD（COPD-BBS）相关的基因中的 rs4986790 和 rs4986791 与 COPD 的关联，并评估风险基因型是否影响细胞因子血清水平。
我们招募了 2092 名参与者，并根据他们的环境暴露情况将他们分为两组进行比较。SNP 采用 TaqMan 探针进行基因分型。通过 ELISA 定量检测血清细胞因子水平（IL-4、IL-5、IL-6、IL-10 和 INF-γ）。
COPD-TS 中的 rs4986790 AA 基因型与更高的 COPD 风险相关（OR=3.53）。单倍型分析证实了这种关联，确定了包含 rs4986790 等位基因的块（A-C，OR=3.11）。与不患 COPD 的吸烟者（SWOC）相比，COPD-TS 表现出更高的 IL-6、IL-4 和 IL-5 水平，而 COPD-BBS 则表现出更高的 IFN-γ、IL-6 和 IL-10 水平。COPD-TS 组中的 AA 携带者与 AG 或 GG 携带者相比，IL-4、IL-5 和 IFN-γ 水平升高。
rs4986790 常见等位基因和 A-C 单倍型（rs4986790-rs4986791）与吸烟者中更高的 COPD 风险相关；携带 AA 基因型的 COPD 患者表现出更多的促炎细胞因子。
