TNF-α and IL-1RA Polymorphisms and Silicosis Susceptibility in Chinese Workers Exposed to Silica Particles: A Case-Control Study.

Abstract: Objective: To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods: Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α (−238 and −308) and IL-1RA (+2018) was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) and SYBR green-based quantitative polymerase chain reaction (qPCR), respectively. Unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidential intervals (CI) for SNPs. Results: No significant differences were found between cases and controls in particles exposure length, body mass index (BMI), and status of smoking and alcohol consumption except for age (P=0.001) and blood type (P=0.042). The frequencies of TNF-α (−238) and IL-1RA (+2018) genotypes in cases were significantly different from those in controls, (P=0.001 and P=0.002, respectively), while a borderline significant difference was found in the frequencies of TNF-α (−308) between cases and controls (P=0.063). The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNF-α (−308), TNF-α (−238) and IL-1RA (+2018) were 2.8 (95% CI: 1.1–7.5), 20.9 (95% CI: 1.8–236.4) and 4.0 (95% CI: 1.6–10.1), respectively. Conclusion: It is suggested that cytokine polymorphisms of TNF-α (−238, −308) and IL-1RA (+2018) are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted. [Copyright &y& Elsevier]