The overall kinome density is in good agreement with taxonomy

CC/CT genotype compared to ATA patients.29 These data suggest that SNPs on the PTGERs genes might exert their genetic effect through coordination of each gene. THROMBOXANE A SYNTHASE 1 and THROMBOXANE A2 RECEPTOR: Thromboxane A2 induces bronchoconstriction and bronchial hyper-responsiveness and stimulates proliferation of human airway smooth muscle cells and immune cells.31 Metabolites of thromboxane increase in the urine and airways of PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19805400 AIA compared to ATA in the basal condition before aspirin challenge.32 Aspirin challenge decreases concentrations of thromboxane B2 in asthmatics. Thromboxane synthase catalyzes the conversion of prostaglandin H to thromboxane A2. A genetic variant study of a Korean population demonstrated that the frequency of the minor allele +141931T>A in intron 9 was MedChemExpress PP 242 significantly lower in the AIA than the ATA groups. AA carriers of +141931T>A had significantly lower plasma TXB2 levels than TT carriers. The mRNA levels of the full-length wild-type and an exon-12-deleted splice variant were significantly higher in the TT than in the AA homozygotes of +141931T>A. Based on these data, it appears that the minor allele of rs6962291 may protect against aspirin hypersensitivity via a lower catalytic activity of the TBXAS1 gene, itself attributable to an increased nonfunctioning isoform of TBXAS1.33 TXA2 exerts its effects by interacting with the G protein-coupled TBXA2R. Genetic association studies have identified a positive association between TBXA2R polymorphisms and the risk of asthma, atopy, and atopic dermatitis.34,35 The minor C allele frequency of TBXA2R rs11085026 on exon 3 was significantly higher in AIA than in ATA.36 The association was validated in another Korean AIA population. Of the three SNPs rs4807491, +795T>C, and R343Q of TBXA2R, one SNP in the promoter area and one non-synonymous coding SNP in exon 3 were significantly associated with the AIA phenotype. The fre- 262 http://e-aair.org Allergy Asthma Immunol Res. 2013 September;5:258-276. http://dx.doi.org/10.4168/aair.2013.5.5.258 AAIR quency of CC homozygote in -4684C>T on the promoter in the AIA patients was one-half and that of CC homozygote in 795T>C was two times higher in the AIA patients compared to those in the ATA patients.29 REGULATOR OF G PROTEIN SIGNALING 7-BINDING PROTEIN: G protein coupled receptors mediate cellular responses to diverse signals, including neurotransmitters, hormones, and sensory stimuli. Many arachidonic acid metabolites signal via GPCRs, including CysLTR1 and 2, prostaglandin D2 receptor, PTGERs, TBXA2R, and M2 muscarinic receptor. These receptors have seven membrane-spanning regions and interact with intracellular, heterotrimeric G proteins, which comprise,, and subunits and play a critical role in signal transduction by coupling extracellular receptors to intracellular signaling pathways.37 Signal-regulated palmitoylation of RGS7BP initiates the activation of GPCRs via regulation of RGS-binding proteins.38 Thus, genetic alterations in the RGS7BP gene may induce functional changes in GPCRs, including the M2 muscarinic receptor, as well as others, including those through which CysLTs, prostaglandins, lipoxins, and thromboxanes signal. In a Korean population, a haplotype of block 3, consisting of the minor alleles +98092C >G, +98853C>T in intron 5, and +104450T>G in the 3UTR of the RGS7BP gene, was associated with AERD. The log-transformed provocation concentration that caused a decrease in forced expiratory volume in 1 seco