|
| Gene name | SNPs | Clinical Phenotype | Mechanism |
|
| Leukotriene synthesis | |
| LTC4S | −444A > C | C allele had high genotype frequency compared with A allele | C allele may be the risk allele due to overproduction of CysLTs |
| ALOX5 | −1708G > A, 21C > T, 270G > A, 1728G > A | ALOX5 ht1(GCGA) had higher haplotype frequency | ALOX5 ht1(GCGA) may be the risk haplotype |
| CYSLTR1 | −634C > T, −475A > C, −336A > G | ht2(TCG) showed higher frequency in AERD and higher promoter activity | Higher CysLTR1 mRNA expression may be responsible for pathogenesis |
| CYSLTR2 | −819T > C | the frequencies of rare allele were increased in AERD and fall in FEV1 after aspirin provocation | Elevation of CysLTs production |
|
| COX/PG pathway and HLA allele | |
| PTGER | rs7543182 rs959 | These two polymorphisms retained their susceptibility to aspirin intolerance in first and second cohorts | PTGER3 might play a significant role in aspirin hypersensitivity |
| TBXA2R | +795T > C | AERD patients with homozygous +795 C allele had a greater percent fall in FEV1 after aspirin exposure compared with TBXA2R+795 CT or TT genotypes. | TBXA2R+795T > C may increase bronchoconstrictive response to ASA |
| HLA | DPB1*0301 | Patients with DPB1*0301 allele had higher prevalence of Rhino-sinusitis and lower FEV1 values. | HLA markers may be important for LTRA therapy |
| Gene name | SNPs | Clinical Phenotype | Mechanism |
|
| Eosinophil activation | |
| CRTH2 | −466T > C | −466T allele had higher frequency in AERD and increased serum, cellular eotaxin-2 production and lower mRNA expression | −466T allele may be the risk allele by activation of eosinophils |
| CCR3 | −520T > C | The frequencies of rare genotypes were higher in AERD and −520G allele showed higher promoter activity | Higher mRNA expression of CCR3 may cause eosinophil activation |
| IL 13 | 1510A > C, 1055C > T, Arg110Gln | Increase eotaxin-1 and peripheral eosinophil count | Eosinophil activation may occur |
|
| Mast cell activation | |
| FCERIG | −237A > G −344C > T | AA type of −237A > G showed high serum total IgE; CC/CT of −344C/T had higher SEA | Mast cells may be activated |
| MS4A2R | E237G | FcER1b −109T allele had higher frequency and high promoter activity | Increased mRNA expression of −109T allele may cause mast cell activation mediated by MS4A2R receptor |
|
| Other mechanisms | | |
| IL-10 and TGF-β1 | −1082 A > G and −509C > T | The frequency of rare alleles (the CT or TT genotype of TGF-β1) 509C/T and AG or GG genotype of (IL-10 )1082A/G was significantly higher in AERD and −1082G had higher promoter activity | Alteration in IL-10 production caused by the −1082A/G in IL-10 may contribute to disease pathogenesis which is strengthened by a genetic interaction with TGF-β1. |
| ACE | −262A > T, −115T > C | The frequencies of the rare alleles were higher in AERD −262T had lower promoter activity and fall of FEV1 after aspirin provocation | Downregulation of ACE expression |
| KIF3A | rs 3756775 | Fall of FEV1 and higher mRNA expression of KIF3A in the ASA induced bronchial epithelial cells and protein expression in nasal polyp epithelia in AERD | Abnormality of cilia predisposing to AERD |
| SLC6A12 | rs499368, rs557881 | The minor allele frequencies were higher in AERD and fall of FEV1 after aspirin provocation | GABA signaling pathway in the airway epithelium may play a role |
| CEP68 | 7572857G > A | Fall of FEV1 after aspirin provocation by A allele | Change in polarity of the protein structure due to nonsynonymous SNP which replaces Gly with Ser |
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