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 Fc ɛ RI-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-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.