ty to AIA.110 IL-10 and TGF-1: AIA is characterized by excessive proliferation of target tissues such as eosinophilic rhinosinusitis and nasal polyposis. The TGF-1 -509 C>T polymorphism on the promoter is associated with rhinosinusitis in AIA patients.111 The regulatory function of TGF-1 is interrelated with IL-10.112 A gene-gene interaction between TGF-1 and IL-10 polymorphisms has also been AZD-0530 site 
implicated in allergy and asthma.113 The IL-10 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19805400 haplotype is considered to be a risk haplotype in atopic asthmatics in North India.114 The IL10 ATA haplotype was associated with reduced IL-10 production observed in severe asthma.115 Furthermore, the -1082A>G of IL-10 was significantly associated with the AIA phenotype. Moreover, a synergistic effect between TGF-1 -509 C>T and IL-10 -1082 A>G has been observed in the AIA phenotype. The frequency of minor alleles was three times higher in patients with AIA than in those with ATA.116 Volume 5, Number 5, September 2013 sinogen gene enhances the effect of several bronchoconstrictors and produces angiotensin in the airways of asthmatics. Of 38 SNPs in the AGT gene, two in the AGT intron were significantly associated with modification of a long-term leukotriene-receptor antagonist effect. However, these data are preliminary, and a larger-scale study is warranted. STRUCTURAL VARIATION AND EPIGENESIS IN AERD GENETICS Previous epidemiologic studies have demonstrated that SNPs are not responsible for all differences in phenotype. Because monozygotic twins are genetically identical, asthma develops almost concurrently. However, a twin cohort study showed one fifth of concordance rate of self-reported asthma in monozygotic twin pairs.123 A possible explanation for this is epigenesis. Epigenetics is the study of heritable changes in DNA structure that do not alter the underlying sequence; well-known examples are DNA methylation and histone modification. These changes may remain through cell divisions for the remainder of the cell’s life and may also last for multiple generations. For example, human epidemiologic studies have shown that the mother’s diet affects her offspring’s risk of allergic asthma.124 It is not known whether exposure to environmental agents induces epigenetic changes in aspirin hypersensitivity. In nasal polyps from subjects with AERD and ATAs, the methylation pattern of 27,168 DNA CpG sites was assessed using a whole-genome methylation analysis.125 Methylation patterns were significantly different in nasal polyps, but not so different in buffy coats. A volcano plot showed differential methylation levels in AERD and ATA: 332 CpG sites on 296 genes were hypomethylated, and 158 sites on 141 genes were hypermethylated. CpG-site methylations in nasal polyps were not correlated with those of buffy coats, indicating that the difference in methylation pattern is nasal-tissue specific. Of the genes in the arachidonate pathway, prostaglandin E synthase was hypermethylated, whereas prostaglandin D synthase, arachidonate 5-lipooxygenase activating protein, leukotriene B4 receptor, and lipoxygenase homology domain1 were hypomethylated, indicating that this may be responsible for the existence of specific phenotypes, such as AERD, in asthma. PHARMACOGENETICS Both augmentation of CysLTs production and overexpression of CysLT receptors on inflammatory cells occur within the respiratory tract in patients with AIA.7,117 The CysLT receptor is selectively antagonized by several currently available leukotriene mo
