title: Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation frequency.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan.|Division of Pulmonary Medicine, Infectious Diseases and Oncology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.|Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Angata
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wan
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan.|Division of Pulmonary Medicine, Infectious Diseases and Oncology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Motegi
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Saitama, Japan.
authors.forename: Congxiao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Analytical biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ohtsubo
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Saitama, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.affiliation: Division of Pulmonary Medicine, Infectious Diseases and Oncology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: University of British Columbia Center for Heart Lung Innovation, University of St Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: ParÉ
authors.affiliation: UCL Respiratory, University College London, London, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Saitama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan.|Division of Pulmonary Medicine, Infectious Diseases and Oncology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Kozui
authors.initials: K
authors.lastname: Kida
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D004247:DNA
keywords: chronic obstructive pulmonary disease; emphysema; genetics; in vitro assays; infection and inflammation