Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and Aspirin exacerbated respiratory diseases

초록

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

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