Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still's Disease

J Immunol Res. 2020 Feb 14;2020:8640719. doi: 10.1155/2020/8640719. eCollection 2020.


Adult-onset Still's disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5'-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P = 1.20 × 10-8, OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n = 82, median: 9.31 pg/mL), particularly in the cases with activity score ≥ 6 (n = 42, 10.94 pg/mL), compared to the healthy donors (n = 68, 5.31 pg/mL) (P < 0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P < 0.0001) or AT genotype (11.61 pg/mL) (P = 0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD.

MeSH terms

  • Adult
  • Alleles
  • Female
  • Gene Expression*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Macrophage Colony-Stimulating Factor / blood
  • Macrophage Colony-Stimulating Factor / genetics*
  • Macrophage Colony-Stimulating Factor / metabolism
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Still's Disease, Adult-Onset / diagnosis*
  • Still's Disease, Adult-Onset / genetics*


  • CSF1 protein, human
  • Macrophage Colony-Stimulating Factor