Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency

Respirology. 2017 May;22(4):684-690. doi: 10.1111/resp.12952. Epub 2016 Nov 22.


Background and objective: The exacerbation-prone phenotype of COPD is particularly important, as exacerbations lead to poor quality of life and disease progression. We previously found that COPD patients who lack Siglec-14, a myeloid cell protein that recognizes bacteria and triggers inflammatory responses, are less prone to exacerbation. We hypothesized that the variations in other SIGLEC genes could also influence COPD exacerbation frequency, and investigated the association between SIGLEC9 polymorphisms and the exacerbation-prone phenotype of COPD.

Methods: We examined whether SIGLEC9 polymorphisms affect the frequency of COPD exacerbation in 135 subjects within our study population, and also analysed the correlation between the genotypes and the severity of airflow obstruction and emphysema in 362 Japanese smokers including 244 COPD patients. The association between these single nucleotide polymorphisms (SNPs) and COPD phenotypes were also assessed in a Caucasian population of ECLIPSE study. The effects of these coding SNPs (cSNPs) on Siglec-9 protein functions were analysed using in vitro assays.

Results: The G allele of rs2075803 and rs2075803 G/rs2258983 A(GA) haplotype in SIGLEC9 was associated with higher frequency of exacerbations and the extent of emphysema in COPD. These results did not replicate in the ECLIPSE study. A myeloid cell line expressing the Siglec-9 variant corresponding to GA haplotype produced more TNF-α than the one expressing the variant corresponding to the other major haplotype.

Conclusion: The SIGLEC9 rs2075803 G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less effective at suppressing inflammatory response, may be a risk factor for the development of emphysema.

Trial registration: NCT00292552.

Keywords: chronic obstructive pulmonary disease; emphysema; genetics; in vitro assays; infection and inflammation.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • DNA / genetics*
  • Disease Progression
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Recurrence
  • Sialic Acid Binding Immunoglobulin-like Lectins / genetics*
  • Sialic Acid Binding Immunoglobulin-like Lectins / metabolism


  • Antigens, CD
  • SIGLEC9 protein, human
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • DNA

Associated data