title: Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Kanagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Motohiro
authors.initials: M
authors.lastname: Ebisawa
authors.forename: Morimitsu
authors.initials: M
authors.lastname: Tomikawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Imai
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Komata
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.forename: Michishige
authors.initials: M
authors.lastname: Harada
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sakashita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimojo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kohno
authors.forename: Kimie
authors.initials: K
authors.lastname: Fujita
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyatake
authors.forename: Satoru
authors.initials: S
authors.lastname: Doi
authors.forename: Tadao
authors.initials: T
authors.lastname: Enomoto
authors.forename: Masami
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Noritaka
authors.initials: N
authors.lastname: Higashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
mesh_terms: D000483:Alleles; D000707:Anaphylaxis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D001241:Aspirin