POLYMORPHISMS IN THE PROMOTER OF THE TUMOR-NECROSIS-FACTOR-ALPHA GENEIN COAL-MINERS

Tumor necrosis factor-alpha (TNF) is recognized as a central mediator of mineral dust-induced lung fibrosis, and genetic polymorphisms of th e TNF promoter have been reported to influence levels of TNF productio n. To assess whether polymorphisms within the TNF promoter gene are as sociated with susceptibility to coal workers' pneumoconiosis (CWP), th e 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 com pared with miners without CWP (25%) and controls (29%). After correcti on for cumulative dust exposure and smoking, the A(-308) transition ge notype 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 d ust-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 scre ening to estimate individual health risks for effects of coal mine dus t exposure. (C) 1998 Wiley-Liss, Inc.