Polymorphisms in autophagy related genes and the coal workers' pneumoconiosis in a Chinese population
2017
Yuan, Jiali | Han, Ruhui | Esther, Ayaaba | Wu, Qiuyun | Yang, Jingjin | Yan, Weiwen | Ji, Xiaoming | Liu, Yi | Li, Yan | Yao, Wenxi | Ni, Chunhui
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 (ATGs) and the risk of coal workers' pneumoconiosis has not been reported yet. Total of 7 SNPs in ATGs (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 ATGs, which implicated the development of CWP. Further studies are warranted to validate these findings.
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