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The single nucleotide polymorphism CRTh2 rs533116 is associated with allergic asthma and increased expression of CRT h2
Author(s) -
Campos Alberto E.,
MacLean E.,
Davidson C.,
Palikhe N. S.,
Storie J.,
Tse C.,
Brenner D.,
Mayers I.,
Vliagoftis H.,
ElSohemy A.,
Cameron L.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12003
Subject(s) - single nucleotide polymorphism , immunology , allergic inflammation , population , allergy , genotype , asthma , medicine , snp , microbiology and biotechnology , biology , gene , genetics , environmental health
Background CRT h2 (chemoattractant‐receptor homologous molecule expressed on T h2 cells) is expressed by T h2 cells and other cells involved in allergic inflammation. Single nucleotide polymorphisms ( SNP s) in CRTh2 (rs11571288, rs545659, rs634681) have been associated with various phenotypes of allergy in ethnically distinct populations. Here, we assessed the association between CRTh2 rs533116 and allergic asthma, expression of CRT h2 and T h2 cytokine production. Methods CRTh2 rs533116 was genotyped in an ethnically diverse population ( n = 1282). The proportion of cells expressing CRT h2 was determined in peripheral blood from subjects with allergic airways disease and controls as well as with in vitro differentiated T h2 cells. Receptor function was assessed by stimulating T h2 cells with the CRT h2‐specific agonist 13,14‐dihydro‐15‐keto‐ PGD 2 ( DK ‐ PGD 2 ) and measuring IL ‐4 and IL ‐13 by intracellular staining and ELISA . Results CRTh2 rs533116 was associated with allergic asthma in White people (2.67 [1.09–6.55], P < 0.05), and expression of CRT h2 was higher in subjects with allergic airways disease compared to controls ( P < 0.05). Among allergic individuals, the AA genotype was significantly associated with more eosinophils and higher expression of CRT h2 by both CD 4 + T cells and eosinophils ( P < 0.05). In vitro , the AA genotype was associated with a higher proportion of CRT h2 + cells during T h2 differentiation as well as more IL ‐4 and IL ‐13 expression following DK ‐ PGD 2 stimulation ( P < 0.05). Conclusions These findings show an association between CRTh2 rs533116 and allergic asthma and suggest this may be mediated by elevated expression of CRT h2, leading to higher numbers of circulating eosinophils and Th2 cytokine production.