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SOCS-1 is a critical regulator of multiple signaling pathways, including those activated by cytokines that regulate Ig H chain class switching to IgE. Analysis of mice with mutations in the SOCS-1 gene demonstrated that IgE levels increase with loss of SOCS-1 alleles. This suggested that overall SOCS-1 acts as an inhibitor of IgE expression in vivo. A genetic association study was performed in 474 children enrolled in the Tucson Children’s Respiratory Study to determine if genetic variation in the SOCS-1 locus correlates with altered levels of IgE. Carriers of the C-allele for a novel, 3′ genomic single nucleotide polymorphism (SNP) in the SOCS-1 gene (SOCS1+ 1125G> C; rs33932899) were found to have significantly lower levels of serum IgE compared with those of homozygotes for the G-allele. Analysis demonstrated that the SOCS1+ 1125G> C SNP was in complete linkage disequilibrium with an SNP at position …