Differential contribution of the CysLTR1 gene in patients with aspirin hypersensitivity.
In this study, we compared the roles of CysLT receptor type 1 (CysLTR1) and leukotriene C4 synthase (LTC4S) gene polymorphisms in two major aspirin-related allergic diseases, aspirin-intolerant asthma (AIA) and aspirin-induced chronic urticaria/angioedema (AICU). CysLTR1-634C>T and LTC4S-444A>C polymorphisms were genotyped and its functional effect on the promoter activity was compared. As in vivo functional study, changes of peripheral mRNA level of CysLTR1 were measured by real-time PCR before and after aspirin challenge. A significant association was found for the CysLTR1 promoter polymorphism and the AIA phenotype compared to AICU (P = 0.015). In U937 cells, the variant genotype reporter construct showed significantly higher promoter activity than the common genotype (P < 0.05). The CysLTR1 mRNA levels increased significantly after aspirin challenge in AIA patients (P = 0.013). In conclusion, the CysLTR1 polymorphism may contribute to develop to the AIA phenotype and be used as a genetic marker for differentiating two major aspirin hypersensitivity phenotypes.
Kim
Seung-Hyun
SH
Department of Allergy and Rheumatology, Ajou University School of Medicine, San-5, Woncheondong, Youngtonggu, Suwon, Republic of Korea.
Yang
Eun-Mi
EM
Park
Han-Jung
HJ
Ye
Young-Min
YM
Lee
Hyun-Young
HY
Park
Hae-Sim
HS
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018077:Receptors, Leukotriene / Q000235:genetics*; D020298:U937 Cells; D014581:Urticaria / Q000235:genetics / Q000276:immunology
D005819:Genetic Markers; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C083169:leukotriene D4 receptor; D001241:Aspirin