Polymorphisms in autophagy related genes and the coal workers' pneumoconiosis in a Chinese population.

Autophagy is an evolutionary conserved intracellular degradation/recycling system that is essential for cellular homeostasis. Dysregulation of this process leads to a number of disorders, including pulmonary fibrosis. However, the genetic association between singe nucleotide polymorphisms of autophagy related genes ( ATG s) and the risk of coal workers' pneumoconiosis has not been reported yet. Total of 7 SNPs in ATG s ( ATG16 , ATG12 , ATG5 , ATG10 ) were investigated for their roles in CWP by a case-control study which including 705 CWP patients and 703 control subjects. Genotyping were performed by the Sequenom Mass ARRAY system. Luciferase assays were taken to test the effects of rs26538 C > T on the activity of ATG12 in the promoter. Our data showed that ATG10 rs1864182 GT genotype was associated with a decreased risk of CWP compared with TT genotype (OR = 0.42, 95% CI = 0.33–0.54, P = 0.001). Another 2 SNPs (rs26538, rs510432) were also with the marked decreases in the risk of CWP under recessive models (OR = 0.58, 95% CI = 0.40–0.83, P = 0.002 for rs26538; OR = 0.74, 95% CI = 0.57–0.97, P = 0.040 for rs510432). Luciferase assays in two different cell lines revealed that the rs26538 C > T substitution could reduce the expression of ATG12 . Taken together, we identified three SNPs in ATG s, which implicated the development of CWP. Further studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]