A SOCS-1 promoter variant is associated with total serum IgE levels

Justin Mostecki, Suzanne L. Cassel, Walter T. Klimecki, Debra A. Stern, Judit Knisz, Sachiyo Iwashita, Penelope Graves, Rachel L. Miller, Maartje Van Peer, Marilyn Halonen, Fernando D. Martinez, Donata Vercelli, Paul B. Rothman

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13 Scopus citations

Abstract

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, 39 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 SOCS12820G > T (rs33977706) of the SOCS-1 promoter. Carriers of the T-allele at the SOCS1-820G > T were also found to be associated with the decreased IgE. The promoter SNP increased transcriptional activity of the SOCS-1 promoter in reporter assays and human B cells. Consistent with this observation, the presence of this polymorphism within the promoter abolished binding of yin yang-1, which is identified as a negative regulator of SOCS-1 transcriptional activity. These data suggest that genetic variation in the SOCS-1 promoter may affect IgE production.

Original languageEnglish (US)
Pages (from-to)2794-2802
Number of pages9
JournalJournal of Immunology
Volume187
Issue number5
DOIs
StatePublished - Sep 1 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mostecki, J., Cassel, S. L., Klimecki, W. T., Stern, D. A., Knisz, J., Iwashita, S., Graves, P., Miller, R. L., Van Peer, M., Halonen, M., Martinez, F. D., Vercelli, D., & Rothman, P. B. (2011). A SOCS-1 promoter variant is associated with total serum IgE levels. Journal of Immunology, 187(5), 2794-2802. https://doi.org/10.4049/jimmunol.0902569