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- Title
Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma.
- Authors
Pei-Song Gao; Shimizu, Kenichi; Grant, Audrey V.; Rafaels, Nicholas; Lin-Fu Zhou; Hudson, Sherry A.; Konno, Satoshi; Zimmermann, Nives; Araujo, Maria I.; Ponte, Eduardo V.; Cruz, Alvaro A.; Nishimura, Masaharu; Song-Nan Su; Nobuyuki Hizawa; Beaty, Terry H.; Mathias, Rasika A.; Rothenberg, Marc E.; Barnes, Kathleen C.; Bochner, Bruce S.
- Abstract
Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) promotes the apoptosis of eosinophils and inhibits FcɛRI-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-sLex, 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.
- Subjects
GENETIC polymorphisms; SIALIC acids; IMMUNOGLOBULINS; ASTHMA; APOPTOSIS
- Publication
European Journal of Human Genetics, 2010, Vol 18, Issue 6, p713
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/ejhg.2009.239