Wei Wang1, Yuhui Yu2, Shuangshuang Wu3, Lingli Sang2, Xiaohui Wang2, Anni Qiu2, Xiaoqiao Yu2, Jingzhi Li2, Lu Zhang2, Min Yi2, Huiting Zheng2, Yuexia Gao2, Jing Xiao2, Yihua Lu2, Liying Jiang2, Yulong Lian2, Xun Zhuang4, Tian Tian5, Minjie Chu6. 1. School of Public Health, Nantong University, Nantong, China; Department of Occupational Health, Center for Disease Control and Prevention of Wuxi, Wuxi, China. 2. School of Public Health, Nantong University, Nantong, China. 3. Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China. 4. School of Public Health, Nantong University, Nantong, China. Electronic address: ntzhuang@163.com. 5. School of Public Health, Nantong University, Nantong, China. Electronic address: ttyes_01@163.com. 6. School of Public Health, Nantong University, Nantong, China. Electronic address: chuminjie@ntu.edu.cn.
Abstract
BACKGROUND: Two recent genome-wide association studies (GWASs) reported that the FAM13A gene at the 4q22 locus associated with pulmonary fibrosis (defined by rs2609255) overlapping with COPD (defined by rs6837671). We hypothesized that single-nucleotide polymorphisms (SNPs) related to lung disease (especially pulmonary fibrosis) identified in this region are also associated with the risk of silicosis. METHODS: To test this hypothesis, we genotyped these two SNPs (rs2609255 and rs6837671) in a case-control study including 177 silicosis cases and 204 controls with silica dust exposure years similar to the levels for cases in a Chinese population. RESULTS: We found that rs2609255 was significantly associated with increased silicosis risk (dominant model: OR = 1.71; 95% CI = 1.01-2.92; P = 0.047). Additionally, eQTL analysis based on the GTEx database indicated that the rs2609255 polymorphism may alter the expression level of FAM13A in lung tissues (P = 1.8 × 10-4). Furthermore, interaction analyses showed that rs2609255 interacts multiplicatively with years of silica dust exposure to contribute to silicosis risk (interaction P = 0.040). CONCLUSIONS: These results indicate that rs2609255 may modify silicosis susceptibility in the Chinese population.
BACKGROUND: Two recent genome-wide association studies (GWASs) reported that the FAM13A gene at the 4q22 locus associated with pulmonary fibrosis (defined by rs2609255) overlapping with COPD (defined by rs6837671). We hypothesized that single-nucleotide polymorphisms (SNPs) related to lung disease (especially pulmonary fibrosis) identified in this region are also associated with the risk of silicosis. METHODS: To test this hypothesis, we genotyped these two SNPs (rs2609255 and rs6837671) in a case-control study including 177 silicosis cases and 204 controls with silica dust exposure years similar to the levels for cases in a Chinese population. RESULTS: We found that rs2609255 was significantly associated with increased silicosis risk (dominant model: OR = 1.71; 95% CI = 1.01-2.92; P = 0.047). Additionally, eQTL analysis based on the GTEx database indicated that the rs2609255 polymorphism may alter the expression level of FAM13A in lung tissues (P = 1.8 × 10-4). Furthermore, interaction analyses showed that rs2609255 interacts multiplicatively with years of silica dust exposure to contribute to silicosis risk (interaction P = 0.040). CONCLUSIONS: These results indicate that rs2609255 may modify silicosis susceptibility in the Chinese population.
Authors: K Michael Pollard; David M Cauvi; Jessica M Mayeux; Christopher B Toomey; Amy K Peiss; Per Hultman; Dwight H Kono Journal: Annu Rev Pharmacol Toxicol Date: 2020-08-28 Impact factor: 13.820