A Genetic Variant in the Promoter of the Siglec8 Gene is Associated with Wheeze in a Brazilian Population

RATIONALE:Siglec8, encoding sialic acid binding immunoglobulin like lectin (Siglec)-8, has been suggested to play a role in apoptosis of eosinophils. We investigated the genetic association of sequence variants in the Siglec8 gene with eosinophil-mediated parasitic infestation and allergic disease in a Brazilian population.METHODS: A total of seven Siglec8 haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected and genotyped using TaqMan™ among 356 nuclear Brazil families from the Conde District, Bahia, an area endemic for Schistosoma mansoni. A test was performed for linkage and association to single markers for different phenotypic characteristics using Family-Based Association Test program (FBAT).RESULTS: All seven SNPs, including the coding-region sequence variant rs10409962, which causes a Ser-to-Pro substitution at amino acid 170 (S170P), are common variants with the lowest Minor Allelic Frequency (MAF) at 17% and in Hardy-Weinberg equilibrium in the Brazilian population. Two SNPs [ra10409962 (S170P) and rs10420357A/T] were in strong linkage disequilibrium (D' = 0.89) in this Brazilian population. Family-based association tests of individual SNPs with the phenotypic traits demonstrated significant evidence of linkage to wheeze for the rs36498 T allele (p = 0.013), and suggestive evidence for rs10409962 allele G (P = 0.085) under the recessive model. No significant association was observed for the other phenotypes tested, such as total serum levels of IgE and S. mansoni egg counts in stool.CONCLUSIONS: The current findings indicate that a Siglec8 variant may influence reactive airway inflammation, suggesting a potential role for Siglec8 in the etiology of airway disease like asthma. Further research is needed to elucidate the functional significance of these single-nucleotide polymorphisms. RATIONALE:Siglec8, encoding sialic acid binding immunoglobulin like lectin (Siglec)-8, has been suggested to play a role in apoptosis of eosinophils. We investigated the genetic association of sequence variants in the Siglec8 gene with eosinophil-mediated parasitic infestation and allergic disease in a Brazilian population. METHODS: A total of seven Siglec8 haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected and genotyped using TaqMan™ among 356 nuclear Brazil families from the Conde District, Bahia, an area endemic for Schistosoma mansoni. A test was performed for linkage and association to single markers for different phenotypic characteristics using Family-Based Association Test program (FBAT). RESULTS: All seven SNPs, including the coding-region sequence variant rs10409962, which causes a Ser-to-Pro substitution at amino acid 170 (S170P), are common variants with the lowest Minor Allelic Frequency (MAF) at 17% and in Hardy-Weinberg equilibrium in the Brazilian population. Two SNPs [ra10409962 (S170P) and rs10420357A/T] were in strong linkage disequilibrium (D' = 0.89) in this Brazilian population. Family-based association tests of individual SNPs with the phenotypic traits demonstrated significant evidence of linkage to wheeze for the rs36498 T allele (p = 0.013), and suggestive evidence for rs10409962 allele G (P = 0.085) under the recessive model. No significant association was observed for the other phenotypes tested, such as total serum levels of IgE and S. mansoni egg counts in stool. CONCLUSIONS: The current findings indicate that a Siglec8 variant may influence reactive airway inflammation, suggesting a potential role for Siglec8 in the etiology of airway disease like asthma. Further research is needed to elucidate the functional significance of these single-nucleotide polymorphisms.