A Novel Variant of Desmoplakin Is Potentially Associated with Silicosis Risk.

Two genome-wide association studies and one sequencing study have coincidently reported significant associations of single nucleotide polymorphisms (SNPs) in the desmoplakin (DSP) gene with the risk of pulmonary fibrosis (mainly idiopathic pulmonary fibrosis). However, these findings have not been well generalized to occupational pulmonary fibrosis (e.g., silica-related silicosis). We systematically genotyped 8 potentially functional SNPs and the previously reported rs2076295 and rs2744371 in DSP gene region and evaluated the associations between these 10 SNPs and silicosis risk in a case-control study that included 177 silicosis cases and 204 controls with similar numbers of silica dust exposure years as the cases from a Chinese population. Genotyping was performed using the improved multiligase detection reaction multiplex SNP genotyping system. The variant A allele of rs2076304 exhibited significant association with the risk of silicosis (odds ratio = 1.53, 95% confidence interval = 1.03-2.29, p = 0.036). Moreover, significant association was observed between different genotypes of rs2076304 and DSP expression (p = 1.1 × 10-7 ) in 383 normal lung tissues. Further functional annotation indicated that the rs2076304 might influence the binding of RHOXF1. The rs2076304 in DSP gene is associated with a significantly increased risk of silicosis in a Han Chinese population. Further studies are warranted to validate and extend our findings, especially the biological mechanisms of rs2076304 in silicosis susceptibility.