Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and Aspirin exacerbated respiratory diseases
- Abstract
- Aspirin-exacerbated respiratory diseases (AERD) are associated with the metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high-affinity ligand receptor for potent anti-inflammatory lipid metabolites: lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD. We investigated the relationship between single-nucleotide polymorphisms (SNPs) in the FPR2 and AERD. Asthmatics were categorized into AERD <15% decreases in forced expiratory volume in one second (FEV1), and/or naso-ocular reactions after oral aspirin challenge (n=170) and aspirin-tolerant asthma (ATA, n=268). In all, 11 SNPs were genotyped. FPR2 protein expressions on CD14-positive monocytes in peripheral blood were measured using flow cytometric analysis. We performed RT-PCR of the FPR2 mRNA expressed by peripheral blood mononuclear cells. Logistic regression analysis showed that the minor allele frequency of FPR2-4209T>G (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in the ATA group (n=268) (P=0.006, P-corr=0.04, recessive model). The decline of FEV1 after aspirin challenge was significantly lower in the subjects with GG homozygotes of FPR2-4209T>G than those with the other genotypes (P=0.0002). Asthmatic homozygotes for FPR2-4209T>G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2-4209T>G allele (P=0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2-4209T>G. The minor allele at FPR2-4209T>G may have a protective role against the development of AERD, via increase of FPR2 protein expression in inflammatory cells. Journal of Human Genetics (2012) 57, 247-253; doi:10.1038/jhg.2012.12; published online 1 March 2012
- All Author(s)
- H. J. Kim
; S. H. Cho
; J. S. Park
; T. H. Lee
; E. J. Lee
; Y. H. Kim
; S. T. Uh
; I. Y. Chung
; M. K. Kim
; I. S. Choi
; B. L. Park
; H. D. Shin
; C. S. Park
- Issued Date
- 2012
- Type
- Article
- Keyword
- aspirin; asthma; FPR2 (formyl peptide receptor 2); SNPs(single-nucleotide polymorphisms); single-nucleotide polymorphisms; lipoxin a(4) receptor; intolerant; promoter polymorphism; haplotype; diagnosis
- ISSN
- 1434-5161
- Citation Title
- Journal of Human Genetics
- Citation Volume
- 57
- Citation Number
- 4
- Citation Start Page
- 247
- Citation End Page
- 253
- Language(ISO)
- eng
- DOI
- 10.1038/jhg.2012.12
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/851
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