Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma
| Autor: | T.H. Beaty, Ken-ichi Shimizu, Rasika A. Mathias, Sherry A. Hudson, Kathleen C. Barnes, Satoshi Konno, Pei Song Gao, Maria Ilma Araujo, Marc E. Rothenberg, Eduardo Vieira Ponte, Audrey V. Grant, Lin Fu Zhou, Alvaro A. Cruz, Bruce S. Bochner, Nives Zimmermann, Song Nan Su, Nicholas Rafaels, Masaharu Nishimura, Nobuyuki Hizawa |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male SIGLEC8 Adolescent Single-nucleotide polymorphism Genome-wide association study Sialic acid binding Immunoglobulin E Polymorphism Single Nucleotide White People Article Young Adult Asian People Antigens CD Lectins Genetics Humans SNP Genetic Predisposition to Disease Allele Child Genetics (clinical) Genetic association biology Middle Aged Asthma Black or African American Antigens Differentiation B-Lymphocyte Child Preschool Immunology biology.protein Female Brazil Genome-Wide Association Study |
| Zdroj: | European Journal of Human Genetics. 18:713-719 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2009.239 |
| Popis: | Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) promotes the apoptosis of eosinophils and inhibits FcvarepsilonRI-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 x 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. |
| Databáze: | OpenAIRE |
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