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Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma.
Gao, Pei-Song; Shimizu, Kenichi; Grant, Audrey V; Rafaels, Nicholas; Zhou, Lin-Fu; Hudson, Sherry A; Konno, Satoshi; Zimmermann, Nives; Araujo, Maria I; Ponte, Eduardo V; Cruz, Alvaro A; Nishimura, Masaharu; Su, Song-Nan; Hizawa, Nobuyuki; Beaty, Terry H; Mathias, Rasika A; Rothenberg, Marc E; Barnes, Kathleen C; Bochner, Bruce S.
Afiliação
  • Gao PS; Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. pgao1@jhmi.edu
Eur J Hum Genet ; 18(6): 713-9, 2010 Jun.
Article em En | MEDLINE | ID: mdl-20087405
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Antígenos de Diferenciação de Linfócitos B / Antígenos CD / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Lectinas Tipo de estudo: Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: Eur J Hum Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Antígenos de Diferenciação de Linfócitos B / Antígenos CD / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Lectinas Tipo de estudo: Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: Eur J Hum Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido