A SOCS-1 promoter variant is associated with total serum IgE levels.
A SOCS-1 promoter variant is associated with total serum IgE levels.
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DOI：
10.4049/jimmunol.0902569
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发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Rothman PB
中科院分区：
文献类型：
--
作者：
Mostecki J;Cassel SL;Klimecki WT;Stern DA;Knisz J;Iwashita S;Graves P;Miller RL;van Peer M;Halonen M;Martinez FD;Vercelli D;Rothman PB
SOCS-1 is a critical regulator of multiple signaling pathways, including those activated by cytokines that regulate immunoglobulin heavy 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 as compared with homozygotes for the G-allele. Analysis demonstrated that the SOCS1+1125G>C SNP was in complete linkage disequilibrium with a SNP at position SOCS1−820G>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 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.
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