Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma

Pei Song Gao*, Kenichi Shimizu, Audrey V. Grant, Nicholas Rafaels, Lin Fu Zhou, Sherry A. Hudson, Satoshi Konno, Nives Zimmermann, Maria I. Araujo, Eduardo V. Ponte, Alvaro A. Cruz, Masaharu Nishimura, Song Nan Su, Nobuyuki Hizawa, Terry H. Beaty, Rasika A. Mathias, Marc E. Rothenberg, Kathleen C. Barnes, Bruce S. Bochner

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) promotes the apoptosis of eosinophils and inhibits FεRI-dependent mediator release from mast cells. We investigated the genetic association between sequence variants in Siglec-8 and diagnosis of asthma, total levels of serum IgE (tIgE), and diagnosis of eosinophilic esophagitis (EE) in diverse populations. The effect of sequence variants on Siglec-8 glycan ligand-binding activity was also examined. Significant association with asthma was observed for SNP rs36498 (odds ratios (OR), 0.69, P=8.8 × 10-5) among African Americans and for SNP rs10409962 (Ser/Pro) in the Japanese population (OR, 0.69, P=0.019). Supporting this finding, we observed association between SNP rs36498 and current asthma among Brazilian families (P=0.013). Significant association with tIgE was observed for SNP rs6509541 among African Americans (P=0.016), and replicated among the Brazilian families (P=0.02). In contrast, no association was observed with EE in Caucasians. By using a synthetic polymer decorated with 6′-sulfo-sLe x, a known Siglec-8 glycan ligand, we did not find any differences between the ligand-binding activity of HEK293 cells stably transfected with the rs10409962 risk allele or the WT allele. However, our association results suggest that the Siglec8 gene may be a susceptibility locus for asthma.

Original languageEnglish (US)
Pages (from-to)713-719
Number of pages7
JournalEuropean Journal of Human Genetics
Volume18
Issue number6
DOIs
StatePublished - Jun 1 2010

Keywords

  • Asthma
  • Eosinophilic esophagitis
  • Polymorphisms
  • Sialic acid-binding immunoglobulin-like lectin-8 (Siglec8)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Gao, P. S., Shimizu, K., Grant, A. V., Rafaels, N., Zhou, L. F., Hudson, S. A., Konno, S., Zimmermann, N., Araujo, M. I., Ponte, E. V., Cruz, A. A., Nishimura, M., Su, S. N., Hizawa, N., Beaty, T. H., Mathias, R. A., Rothenberg, M. E., Barnes, K. C., & Bochner, B. S. (2010). Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. European Journal of Human Genetics, 18(6), 713-719. https://doi.org/10.1038/ejhg.2009.239