Department of Molecular Biology and Genetics, School of Biomedicine, Mongolian National University of Medical Sciences, Ulaanbaatar City, Mongolia.
Department of Pulmonology and Allergology, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar City, Mongolia.
PLoS One. 2024 May 21;19(5):e0301807. doi: 10.1371/journal.pone.0301807. eCollection 2024.
Determining SNP-SNP interaction of the disease has become important for further investigation of pathogenesis and experimental research. Although many studies have been published on the effect of MMPs gene polymorphisms on chronic obstructive pulmonary disease (COPD), there is a lack of information on SNP-SNP and SNP-environment interactions. This study aimed to investigate the interaction between the polymorphisms of MMP1, MMP2, MMP9 and MMP12 genes and its combined effect with smoking on the risk of developing COPD. Totally 181 COPD patients and 292 healthy individuals were involved. Blood samples from the participants were tested for genotyping and data were collected through questionnaires. Genotyping was performed with nested allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SNP-SNP and SNP-environment interactions were investigated using multifactor dimensionality reduction and logistic regression analysis. The result showed that participants with high nicotine dependence and heavy smokers had a higher risk of COPD than non-smokers. Also, G/G genotype (cOR = 5.83; 95% CI, 1.19-28.4, p = 0.029) of MMP2 rs243864 and T/T genotype (cOR = 1.79; 95% CI, 1.16-2.76, p = 0.008) of MMP12 rs652438 independently contributes to the susceptibility of COPD. For SNP-SNP interaction, the positive interaction between rs243864 G/G genotype of MMP2 and rs652438 T/T genotype of MMP12 was found, and the combination of risk genotypes has a high risk of COPD (OR = 12.92; 95% CI, 1.46-114.4, p = 0.021). Moreover, the combination of T/T genotype of MMP12 rs652438 and smoking-related factors increases the risk of COPD approximately 4.5 to 6-fold. The results suggests that there is a combination of MMP2, MMP12, and smoking-related factors may increase the risk of developing COPD.
确定疾病的 SNP-SNP 相互作用对于进一步研究发病机制和实验研究变得很重要。尽管已经有许多关于 MMPs 基因多态性对慢性阻塞性肺疾病（COPD）影响的研究发表，但关于 SNP-SNP 和 SNP-环境相互作用的信息却很少。本研究旨在探讨 MMP1、MMP2、MMP9 和 MMP12 基因多态性之间的相互作用及其与吸烟的联合效应对 COPD 发病风险的影响。共纳入 181 例 COPD 患者和 292 例健康对照者。采集参与者的血样进行基因分型，并通过问卷收集数据。采用巢式等位基因特异性聚合酶链反应（AS-PCR）和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。采用多因素降维分析和逻辑回归分析来研究 SNP-SNP 和 SNP-环境相互作用。结果显示，尼古丁依赖程度高和重度吸烟者患 COPD 的风险高于不吸烟者。此外，MMP2 rs243864 的 G/G 基因型（cOR=5.83；95%CI，1.19-28.4，p=0.029）和 MMP12 rs652438 的 T/T 基因型（cOR=1.79；95%CI，1.16-2.76，p=0.008）与 COPD 的易感性独立相关。对于 SNP-SNP 相互作用，发现 MMP2 rs243864 的 G/G 基因型和 MMP12 rs652438 的 T/T 基因型之间存在阳性相互作用，并且风险基因型的组合具有较高的 COPD 发病风险（OR=12.92；95%CI，1.46-114.4，p=0.021）。此外，MMP12 rs652438 的 T/T 基因型与与吸烟相关的因素相结合，可使 COPD 的发病风险增加约 4.5 至 6 倍。研究结果表明，MMP2、MMP12 和与吸烟相关的因素的组合可能会增加患 COPD 的风险。
