Document Detail

Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma.
MedLine Citation:
PMID:  19767079     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: NLR family, pyrin domain containing 3 (NLRP3), controls the activity of inflammatory caspase-1 by forming inflammasomes, which leads to cleavage of the procytokines IL-1beta and IL-18. Recent studies have shown associations of human NLRP3 polymorphisms with susceptibility to various inflammatory diseases; however, the association with allergic diseases remains unclear. OBJECTIVE: We sought to examine whether NLRP3 polymorphisms are associated with susceptibility to food allergy, food-induced anaphylaxis, and aspirin-induced asthma (AIA). METHODS: We selected 15 tag single nucleotide polymorphisms (SNPs) of NLRP3 and conducted association analyses of NLRP3 using 574 and 1279 samples for food allergy and AIA, respectively. We further performed functional analyses of the susceptible SNPs. RESULTS: Two NLRP3 SNPs (rs4612666 and rs10754558) were significantly associated with susceptibility to food-induced anaphylaxis (P = .00086 and P = .00068, respectively). The NLRP3 haplotype of the 2 SNPs also showed a significant association (P = .000098). We could confirm the association with susceptibility to another hypersensitivity phenotype, AIA (rs4612666, P = .0096). Functional analysis revealed that the risk alleles of rs4612666 and rs10754558 increased the enhancer activity of NLRP3 expression and NLRP3 mRNA stability, respectively. CONCLUSION: Our results indicate that the NLRP3 SNPs might play an important role in the development of food-induced anaphylaxis and AIA in a gain-of-function manner. Further research on the NLRP3 inflammasome will contribute to the development of novel diagnostic and therapeutic methods for food-induced anaphylaxis and AIA.
Yuki Hitomi; Motohiro Ebisawa; Morimitsu Tomikawa; Takanori Imai; Takatsugu Komata; Tomomitsu Hirota; Michishige Harada; Masafumi Sakashita; Yoichi Suzuki; Naoki Shimojo; Yoichi Kohno; Kimie Fujita; Akihiko Miyatake; Satoru Doi; Tadao Enomoto; Masami Taniguchi; Noritaka Higashi; Yusuke Nakamura; Mayumi Tamari
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-19
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  124     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-09     Completed Date:  2009-11-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  779-85.e6     Citation Subset:  AIM; IM    
Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Kanagawa, Japan.
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MeSH Terms
Anaphylaxis / genetics*,  immunology,  metabolism
Aspirin / adverse effects*
Carrier Proteins / genetics*,  metabolism
Child, Preschool
Drug Hypersensitivity / genetics*,  immunology,  metabolism
Exons / genetics
Food Hypersensitivity / genetics*,  immunology,  metabolism
Gene Frequency / genetics*
Genetic Predisposition to Disease*
Haplotypes / genetics
Introns / genetics
Polymorphism, Single Nucleotide
Reg. No./Substance:
0/Carrier Proteins; 0/NLRP3 protein, human; 50-78-2/Aspirin

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