Zhai R, Jetten M, Schins R P, Franssen H, Borm P J
Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands.
Am J Ind Med. 1998 Oct;34(4):318-24. doi: 10.1002/(sici)1097-0274(199810)34:4<318::aid-ajim4>3.0.co;2-o.
Tumor necrosis factor-alpha (TNF) is recognized as a central mediator of mineral dust-induced lung fibrosis, and genetic polymorphisms of the TNF promoter have been reported to influence levels of TNF production. To assess whether polymorphisms within the TNF promoter gene are associated with susceptibility to coal workers' pneumoconiosis (CWP), the DNA of 78 coal miners was typed for G-to-A transitions at positions -238 and -308. Our results show that frequency of A-308 genotype (T2) is significantly overpresented in coal miners with CWP (50%), as compared with miners without CWP (25%) and controls (29%). After correction for cumulative dust exposure and smoking, the A-308 transition genotype is still associated with the presence of CWP (OR = 3.0, 95% CI = 1.0-9.0). Both A-238 and A-308 transition genotypes were related to TNF release from endotoxin-stimulated blood monocytes; only the A-238 transition and not the A-308 transition was associated to coal dust-induced TNF release. In summary, this study shows that the A-308 transition is related to CWP, but this relation is not paralleled by a different TNF release in this genotype. A larger number of patients coupled to frequent TNF release are required to evaluate genotype screening to estimate individual health risks for effects of coal mine dust exposure.
肿瘤坏死因子-α（TNF）被认为是矿物粉尘诱导的肺纤维化的关键介质，据报道TNF启动子的基因多态性会影响TNF的产生水平。为了评估TNF启动子基因内的多态性是否与煤工尘肺（CWP）易感性相关，对78名煤矿工人的DNA进行了-238和-308位点G到A转换的基因分型。我们的结果显示，与无CWP的矿工（25%）和对照组（29%）相比，CWP煤矿工人中A-308基因型（T2）的频率显著过高（50%）。在校正累积粉尘暴露和吸烟因素后，A-308转换基因型仍与CWP的存在相关（OR = 3.0，95%CI = 1.0 - 9.0）。A-238和A-308转换基因型均与内毒素刺激的血液单核细胞释放TNF有关；只有A-238转换而非A-308转换与煤尘诱导的TNF释放相关。总之，本研究表明A-308转换与CWP相关，但该基因型中TNF释放的差异并不与之平行。需要更多患者以及频繁的TNF释放情况来评估基因分型筛查，以估计个体因接触煤矿粉尘而产生健康影响的风险。
