Department of Clinical Laboratory, Kai Luan General Hospital, Tangshan, Hebei, China (mainland).
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China (mainland).
Med Sci Monit. 2020 Apr 25;26:e918709. doi: 10.12659/MSM.918709.
BACKGROUND Previous studies have demonstrated the important role of genetic predisposition in coal workers' pneumoconiosis (CWP) in addition to environmental factors. The pathogenesis of pulmonary fibrosis disease is related to telomere activity. We performed this study to assess the association between genetic variants of telomere-related genes and the risk of CWP. MATERIAL AND METHODS We enrolled 652 CWP Chinese Han patients and 648 dust-exposed controls in this case-control design study, genotyping 8 single-nucleotide polymorphisms (SNPs) including TERT (rs2736100), TERC (rs10936599 and rs12696304), and NAF1 (rs7675998, rs3822304, rs12331717, rs936562 and rs4691896) using the Sequenom MassARRAY system. RESULTS We identified a significant allele association between NAF1 rs4691896 and CWP by comparing patients with controls (22.0% vs. 13.0%, odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.54-2.33, Pc=1.14×10⁻⁸). The genotype frequency of rs4691896 differed significantly between the patients and controls (Pc=1.49×10⁻⁸). In addition, rs4691896 was correlated with CWP in an additive genetic model (OR: 1.96, 95% CI: 1.58-2.44, Pc=8.96×10⁻⁹) and a dominant model (OR: 2.15, 95% CI: 1.70-2.73, Pc=2.39×10⁻⁹). CONCLUSIONS Our study for the first time demonstrates an association between a telomere-related gene (NAF1) and CWP in a Chinese Han population, and provides valuable insight to further understand the possible pathogenetic mechanism of fibrosis in CWP.
先前的研究表明，除了环境因素外，遗传易感性在煤工尘肺（CWP）中也起着重要作用。肺纤维化疾病的发病机制与端粒活性有关。我们进行这项研究是为了评估端粒相关基因的遗传变异与 CWP 风险之间的关联。
在这项病例对照设计研究中，我们纳入了 652 名汉族 CWP 患者和 648 名尘暴露对照，使用Sequenom MassARRAY 系统对 8 个单核苷酸多态性（SNP）进行基因分型，包括 TERT（rs2736100）、TERC（rs10936599 和 rs12696304）和 NAF1（rs7675998、rs3822304、rs12331717、rs936562 和 rs4691896）。
通过比较患者与对照组，我们发现 NAF1 rs4691896 与 CWP 之间存在显著的等位基因关联（22.0%对 13.0%，比值比[OR]：1.89，95%置信区间[CI]：1.54-2.33，Pc=1.14×10⁻⁸）。rs4691896 的基因型频率在患者和对照组之间存在显著差异（Pc=1.49×10⁻⁸）。此外，rs4691896 在加性遗传模型（OR：1.96，95%CI：1.58-2.44，Pc=8.96×10⁻⁹）和显性遗传模型（OR：2.15，95%CI：1.70-2.73，Pc=2.39×10⁻⁹）中与 CWP 相关。
我们的研究首次证明了汉族人群中一个端粒相关基因（NAF1）与 CWP 之间存在关联，并为进一步了解 CWP 纤维化的可能发病机制提供了有价值的见解。
