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

Gene. 2018 Jun 30:661:196-201. doi: 10.1016/j.gene.2018.03.098. Epub 2018 Apr 3.

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.

Keywords: FAM13A; Interaction; Silicosis; rs2609255.

MeSH terms

  • Aged
  • Asian People / genetics
  • Asian People / statistics & numerical data
  • Case-Control Studies
  • China / epidemiology
  • Female
  • GTPase-Activating Proteins / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Silicosis / epidemiology
  • Silicosis / genetics*

Substances

  • FAM13A protein, human
  • GTPase-Activating Proteins