Department of Respiratory and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Department of Immunology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, China.
Inhal Toxicol. 2020 Mar;32(4):170-176. doi: 10.1080/08958378.2020.1764153. Epub 2020 May 14.
High-mobility group box 1 (HMGB1) protein plays an important pathogenic role in various diseases such as pulmonary fibrosis. However, the relationship between variation of gene and susceptibility to coal worker's pneumoconiosis (CWP) remains unclear. The objective of the study was to determine the association between polymorphisms and CWP in Chinese Han population. The genotypes of gene rs1045411, rs2249825, rs1412125 and rs1360485 in 340 CWP patients and 312 healthy controls were determined and serum HMGB1 levels were detected. Our finding showed that the rs1360485 G allele increased the risk of CWP in comparison with A allele ( = 0.005). rs1360485 GG genotype as well as AG+GG genotype increased the risk of CWP in comparison with AA genotype ( = 0.010, = 0.025, respectively). Four haplotypes were identified and we found that the GCTA haplotype was associated with resistance to CWP ( = 0.005), while GCTG haplotype was associated with risk to CWP (<0.001). Meanwhile, multifactor dimensionality reduction (MDR) analysis showed that the interaction between rs1360485 and exposure had the strongest, followed by rs2249825 and rs1412125. This study also found that the serum HMGB1 levels of the case group were significantly higher than that of the control group, and the serum HMGB1 levels of homozygous subjects with rs1360485 mutant were higher than that of the heterozygous wild type, respectively (<0.001). Meanwhile, the levels of HMGB1 with GCTA haplotype was lower than with GCTG haplotype (<0.001) Our findings indicated that gene rs1360485 polymorphism was associated with the susceptibility to CWP in Chinese Han population.
高迁移率族蛋白 B1（HMGB1）蛋白在各种疾病中发挥着重要的致病作用，如肺纤维化。然而，基因变异与煤工尘肺（CWP）易感性之间的关系尚不清楚。本研究的目的是确定基因多态性与中国汉族人群 CWP 的关系。在 340 例 CWP 患者和 312 例健康对照中，检测了基因 rs1045411、rs2249825、rs1412125 和 rs1360485 的基因型，并检测了血清 HMGB1 水平。我们的研究结果显示，与 A 等位基因相比，rs1360485 的 G 等位基因增加了 CWP 的发病风险（=0.005）。与 AA 基因型相比，rs1360485 GG 基因型和 AG+GG 基因型均增加了 CWP 的发病风险（=0.010，=0.025）。鉴定出了 4 种单倍型，我们发现 GCTA 单倍型与 CWP 抗性相关（=0.005），而 GCTG 单倍型与 CWP 易感性相关（<0.001）。同时，多因子降维分析（MDR）表明，rs1360485 与暴露之间的相互作用最强，其次是 rs2249825 和 rs1412125。本研究还发现，病例组的血清 HMGB1 水平明显高于对照组，且 rs1360485 突变纯合子的血清 HMGB1 水平高于杂合野生型，分别（<0.001）。同时，具有 GCTA 单倍型的 HMGB1 水平低于具有 GCTG 单倍型的 HMGB1 水平（<0.001）。我们的研究结果表明，基因 rs1360485 多态性与中国汉族人群 CWP 的易感性有关。
