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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2005-10-19
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pubmed:abstractText |
Atopic dermatitis (AD) is frequently associated with eosinophilia, highly elevated immunoglobulin E (IgE) levels and increased levels of T-helper 2-type (Th2) cytokines in skin lesions due to infiltrating T cells. Interleukin-12 (IL-12), in combination with interferon-gamma (IFN-gamma), inhibits IgE synthesis and Th2 cell function. As the IFN-gamma-inducing cytokines IL-12 and IL-23 utilize IL-12Rbeta1 as part of their receptors, it is possible that polymorphic variants of the IL-12Rbeta1 (IL12RB1) gene might determine an individual's susceptibility to AD. Here, we carried out a systemic search for genetic variants of the human IL12RB1 in Japanese subjects and identified 48 genetic variants. In a case-control association study, we found that promoter polymorphisms -111A/T and -2C/T were significantly associated with an increased risk of AD under a recessive model. The -111T-allele frequency in the independent population of child asthmatics was also much higher than that in the control group. In addition, the -111T/T genotype was progressively more common in AD with high total serum IgE levels in an IgE-level-dependent manner. Deletion analysis of the IL12RB1 promoter suggested that the -265 to -104 region that contained the -111A/T polymorphic site harbored an important regulatory element. Furthermore, we showed that the -111A/T substitution appeared to cause decreased gene transcriptional activity such that cells from -111A/A individuals exhibited higher IL12RB1 mRNA levels than those from -111T allele carriers. Our results suggested that in individuals with the -111T/T genotype, reduced IL-12Rbeta1 expression may lead to increased Th2 cytokine production in the skin and contribute to the development of AD and other subsequent allergic diseases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0964-6906
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pubmed:author |
pubmed-author:AkahoshiMitsuteruM,
pubmed-author:DoiSatoruS,
pubmed-author:EbeKoujiK,
pubmed-author:EnomotoTadaoT,
pubmed-author:HirotaTomomitsuT,
pubmed-author:HitoshiNakashimaN,
pubmed-author:IkezawaZenroZ,
pubmed-author:InomataNaokoN,
pubmed-author:MatsudaAkiraA,
pubmed-author:MiyatakeAkihikoA,
pubmed-author:NakashimaKazukoK,
pubmed-author:ObaraKazuhikoK,
pubmed-author:ShimizuMakikoM,
pubmed-author:ShirakawaTaroT,
pubmed-author:TakahashiNaomiN,
pubmed-author:TamariMayumiM
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3149-59
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16159888-Adolescent,
pubmed-meshheading:16159888-Adult,
pubmed-meshheading:16159888-Cytokines,
pubmed-meshheading:16159888-DNA Primers,
pubmed-meshheading:16159888-Dermatitis, Atopic,
pubmed-meshheading:16159888-Female,
pubmed-meshheading:16159888-Gene Components,
pubmed-meshheading:16159888-Gene Expression Regulation,
pubmed-meshheading:16159888-Gene Frequency,
pubmed-meshheading:16159888-Genetic Predisposition to Disease,
pubmed-meshheading:16159888-Genetic Testing,
pubmed-meshheading:16159888-Genotype,
pubmed-meshheading:16159888-Humans,
pubmed-meshheading:16159888-Immunoglobulin E,
pubmed-meshheading:16159888-Japan,
pubmed-meshheading:16159888-Luciferases,
pubmed-meshheading:16159888-Male,
pubmed-meshheading:16159888-Middle Aged,
pubmed-meshheading:16159888-Polymorphism, Genetic,
pubmed-meshheading:16159888-Polymorphism, Single Nucleotide,
pubmed-meshheading:16159888-Promoter Regions, Genetic,
pubmed-meshheading:16159888-Receptors, Interleukin,
pubmed-meshheading:16159888-Receptors, Interleukin-12,
pubmed-meshheading:16159888-Sequence Analysis, DNA,
pubmed-meshheading:16159888-Th2 Cells
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pubmed:year |
2005
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pubmed:articleTitle |
Association of the IL12RB1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes.
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pubmed:affiliation |
Laboratory of Genetics of Allergic Diseases, SNP Research Center, RIKEN, Kanagawa, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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