title: Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma.
abstract: 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.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. pgao1@jhmi.edu
authors.forename: Pei-Song
authors.initials: PS
authors.lastname: Gao
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Audrey V
authors.initials: AV
authors.lastname: Grant
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rafaels
authors.forename: Lin-Fu
authors.initials: LF
authors.lastname: Zhou
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Hudson
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.forename: Nives
authors.initials: N
authors.lastname: Zimmermann
authors.forename: Maria I
authors.initials: MI
authors.lastname: Araujo
authors.forename: Eduardo V
authors.initials: EV
authors.lastname: Ponte
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Cruz
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
authors.forename: Song-Nan
authors.initials: SN
authors.lastname: Su
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
authors.forename: Terry H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000208:ethnology / Q000235:genetics*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D037102:Lectins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D037102:Lectins; C403967:SIGLEC8 protein, human