Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma.
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.
Gao
Pei-Song
PS
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. pgao1@jhmi.edu
Shimizu
Kenichi
K
Grant
Audrey V
AV
Rafaels
Nicholas
N
Zhou
Lin-Fu
LF
Hudson
Sherry A
SA
Konno
Satoshi
S
Zimmermann
Nives
N
Araujo
Maria I
MI
Ponte
Eduardo V
EV
Cruz
Alvaro A
AA
Nishimura
Masaharu
M
Su
Song-Nan
SN
Hizawa
Nobuyuki
N
Beaty
Terry H
TH
Mathias
Rasika A
RA
Rothenberg
Marc E
ME
Barnes
Kathleen C
KC
Bochner
Bruce S
BS
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
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D037102:Lectins; C403967:SIGLEC8 protein, human