Thus GPR132, in this animal model, appeared to have a detrimental effect on atherosclerosis

anscription factors and that their binding is augmented by aspirin. Viral respiratory infections contribute to allergic sensitization and the development of asthma and exacerbation in subjects with already established asthma. Aspirin hypersensitivity is diminished in some AERD patients during acyclovir treatment of herpes simplex infection.53 In a Korean population, AERD patients had a significantly higher frequency of missense variants “A” allele of rs3775291 than did the ATA group.54 The amino acid change from Leu to Phe results in functional deterioration of TLR3 and predisposes individuals to increased susceptibility to the innate immune response, which may be a cause of viral-induced AERD. NLR FAMILY, PYRIN DOMAIN-CONTAINING 3: A member of the order TG 02 nucleotide-binding domain, leucine-rich repeat-containing family controls the activity of inflammatory caspase-1 by forming inflammasomes. Tight collaboration between pathogen-associated molecular patterns and their receptors initiates an innate immune response, and NLRP3 inflammasomes are activated by pathogen-associated molecular patterns including microbial toxins, live bacteria, and viruses.55 After being activated, NALP3 recruits apoptosis-associated speck-like proteins containing procaspase-1, leading to activation of caspase-1. Activated caspase-1 cleaves the procytokines IL-1b and IL-18 into their active forms. Of 15 tag SNPs of NLRP in a large population, one was significantly associated with AIA. The risk allele of rs4612666 increases the enhancer activity of NLRP3 expression and NLRP3 mRNA stability,56 indicating that the NLRP3 SNP might play an important role in the development of AIA in a gain-of-function manner. Genetic Basis of Aspirin Hypersensitivity Asthma Airway remodeling and fibrosis genes A DISINTEGRIN AND METALLOPROTEINASE DOMAIN 33: ADAM33 is expressed strongly in smooth muscle layers and basement membrane in more than 80% of subjects with asthma but not in normal control subjects, indicating that ADAM33 may be involved in airway remodeling in asthma.57 A genome-wide screen revealed ADAM33 to be a novel asthma-susceptibility gene that plays a role in AHR.58 ADAM33 polymorphisms are associated with asthma susceptibility and airway hyperreactivity in several ethnicities, including the Korean population.59 In a Japanese population, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19803812 of 10 polymorphic sites, the ST+7, V-1, and V5 sites in the AIA group were significantly different from those in the ATA group. Haplotypes of three sites were significantly different in frequency between the AIA and ATA groups, indicating that the ADAM33 sequence variations are likely to correlate with susceptibility to AIA.60 FIBROUS SHEATH-INTERACTIONG PROTEIN 1: With its primary function in protein binding, the FSIP1 gene is expressed in the airway epithelium. FSIP1 is regulated by amyloid beta precursor protein.61 APP is an integral membrane protein expressed in many tissues, particularly in the synapses of neurons. APP is cleaved by ADAM33. Of 66 SNPs in the FSIP1 gene, one was associated with AIA in a Korean population.62 In Asian populations from the International HapMap Project, the FSIP1 gene is in LD with the thrombospondin-1 gene. The THBS1 gene has been implicated in a network underlying the pulmonary response to oxidative stress in asthma.63 Aspirin leads to a reduction in THBS1 levels.64 These data suggest that FSIP1 affects aspirin hypersensitivity in asthma associated with the nearby THBS1 gene. The -466T allele exhibits higher