The rs2609255 polymorphism in the FAM13A gene is reproducibly associated with silicosis susceptibility in a Chinese population

• Published in: Gene 2018-06, Vol.661, p.196-201
• Main Authors: Wang, Wei, Yu, Yuhui, Wu, Shuangshuang, Sang, Lingli, Wang, Xiaohui, Qiu, Anni, Yu, Xiaoqiao, Li, Jingzhi, Zhang, Lu, Yi, Min, Zheng, Huiting, Gao, Yuexia, Xiao, Jing, Lu, Yihua, Jiang, Liying, Lian, Yulong, Zhuang, Xun, Tian, Tian, Chu, Minjie
• Format: Article
• Language: English
• Subjects: Aged; Asian Continental Ancestry Group - genetics; Asian Continental Ancestry Group - statistics & numerical data; Case-Control Studies; China - epidemiology; FAM13A; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; GTPase-Activating Proteins - genetics; Humans; Interaction; Male; Middle Aged; Polymorphism, Single Nucleotide; rs2609255; Silicosis; Silicosis - epidemiology; Silicosis - genetics
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2018.03.098

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. 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. 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). These results indicate that rs2609255 may modify silicosis susceptibility in the Chinese population. •The rs2609255 SNP was significantly associated with increased silicosis risk.•The rs2609255 SNP may alter the expression level of FAM13A in lung tissues.•The rs2609255 SNP may interact multiplicatively with years of silica dust exposure to contribute to silicosis risk.